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Oncogenic regulation and function of keratins 8 and 18

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Summary

Keratin 8 (K8) and keratin 18 (K18) are the most common and characteristic members of the large intermediate filament gene family expressed in ‘simple’ or single layer epithelial tissues of the body. Their persistent expression in tumor cells derived from these epithelia has led to the wide spread use of keratin monoclonal antibodies as aids in the detection and identification of carcinomas. Oncogenes which activateras signal transduction pathways stimulate expression of the K18 gene through transcription factors including members of the AP-1 (jun and fos) and ETS families. The persistent expression of K8 and K18 may reflect the integrated transcriptional activation of such transcription factors and, in the cases of ectopic expression, an escape from the suppressive epigenetic mechanisms of DNA methylation and chromatin condensation. Comparison of the mechanisms of transcriptional control of K18 expression with expression patterns documented in both normal and pathological conditions leads to the proposal that persistent K8 and K18 expression is a reflection of the action of multiple different oncogenes converging on the nucleus through a limited number of transcription factors to then influence the expression of a large number of genes including these keratins. Furthermore, correlation of various tumor cell characteristics including invasive behavior and drug sensitivity with K8 and K18 expression has stimulated consideration of the possible functions of these proteins in both normal development and in tumorigenesis. Recent developments in the analysis of the functions of these intermediate filament proteins provide new insights into diverse functions influenced by K8 and K18.

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References

  1. Fuchs E, Weber K: Intermediate filaments: Structure, dynamics, function, and disease. Ann Rev Biochem 63: 345–382, 1994

    Google Scholar 

  2. Lazarides E: Intermediate filaments as mechanical integrators of cellular space. Nature 28: 249–256, 1980

    Google Scholar 

  3. Oshima RG: Intermediate filament molecular biology. Curr Opin Cell Biol 4: 110–116, 1992

    Google Scholar 

  4. Klymkowsky MW: Intermediate filaments: New proteins, some answers, more questions. Curr Opin Cell Biol 7: 46–54, 1995

    Google Scholar 

  5. McLean WHI, Lane EB: Intermediate filaments in disease. Curr Opin Cell Biol 7: 118–125, 1995

    Google Scholar 

  6. Lane EB: Keratin diseases. Curr Opin Genet Dev 4: 412–418, 1994

    Google Scholar 

  7. Blumenberg M: Molecular biology of human keratin genes. In: Darmon M, Blumenberg M (eds) Molecular Biology of the Skin. Academic Press, San Diego 1–32, 1993

    Google Scholar 

  8. Franke WW, Schiller DL, Moll R, Winter S, Schmid E, Engelbrecht I: Diversity of cytokeratins. J Mol Biol 153: 933–959, 1981

    Google Scholar 

  9. Franke WW, Weber K, Osborn M, Schmid E, Freudenstein C: Antibody to prekeratin: Decoration of tonofilament-like arrays in various cells of epithelial character. Exp Cell Res 116: 429–445, 1978

    Google Scholar 

  10. Bannasch P, Zerban H, Schmid E, Franke WW: Liver tumors distinguished by immunofluorescence microscopy with antibodies to proteins of intermediate-sized filaments. Proc Natl Acad Sci USA 77: 4948–4952, 1980

    Google Scholar 

  11. Jackson BW, Grund C, Schmid E, Burke K, Franke W, Illmensee K: Formation of cytoskeletal elements during mouse embryogenesis intermediate filaments of the cytokeratin type and desmosomes in preimplantation embryos. Differentiation 17: 161–179, 1980

    Google Scholar 

  12. Brulet P, Babinet C, Kemler R, Jacob F: Monoclonal antibodies against trophectoderm-specific markers during mouse blastocyst formation. Proc Natl Acad Sci USA 77: 4113–4117, 1980

    Google Scholar 

  13. Kemler R, Brulet P, Schnebelen MT, Gaillard J, Jacob F: Reactivity of monoclonal antibodies against intermediate filament proteins during embryonic development. J Embryol Exp Morphol 64: 45–60, 1981

    Google Scholar 

  14. Oshima RG: Identification and immunoprecipitation of cytoskeletal proteins from murine extra-embryonic endodermal cells. J Biol Chem 256: 8124–8133, 1981

    Google Scholar 

  15. Oshima RG: Developmental expression of murine extra-embryonic endodermal cytoskeletal proteins. J Biol Chem 257: 3414–3421, 1982

    Google Scholar 

  16. Trevor K, Oshima RG: Preimplantation mouse embryos and liver express the same type I keratin gene product. J Biol Chem 260: 15885–15891, 1985

    Google Scholar 

  17. Brulet P, Jacob F: Molecular cloning of a cDNA sequence encoding a trophectoderm-specific marker during mouse blastocyst formation. Proc Natl Acad Sci USA 79: 2328–2332, 1982

    Google Scholar 

  18. Singer PA, Trevor K, Oshima RG: Molecular cloning and characterization of the Endo B cytokeratin expressed in preimplantation mouse embryos. J Biol Chem 261: 538–547, 1986

    Google Scholar 

  19. Ouellet T, Levac P, Royal A: Complete sequence of the mouse type-II keratin Endo A: Its amino-terminal region resembles mitochodrial signal peptides. Gene 70: 75–84, 1988

    Google Scholar 

  20. Magin TM, Jorcano JL, Franke WW: Cytokeratin expression in simple epithelia. cDNA cloning and sequence characteristics of bovine cytokeratin A (no. 8). Differentiation 30: 254–264, 1986

    Google Scholar 

  21. Romano V, Hatzfeld M, Magin TM, Zimbelmann R, Franke WW, Maier G, Ponstingl H: Cytokeratin expression in simple epithelia. Identification of mRNA coding for human cytokeratin no. 18 by a cDNA clone. Differentiation 30: 244–253, 1986

    Google Scholar 

  22. Morita T, Tondella MLC, Takemoto Y, Hashido K, Ichinose Y, Nozake M, Matsushiro A: Nucleotide sequence of mouse EndoA cytokeratin cDNA reveals polypeptide characteristics of the type-II keratin subfamily. Gene 68: 109–117, 1988

    Google Scholar 

  23. Blumenberg M: Concerted gene duplications in the two keratin gene families. J Mol Evol 27: 203–211, 1988

    Google Scholar 

  24. Tamai Y, Takemoto Y, Matsumoto M, Morita T, Matsushiro A, Nozaki M: Sequence of the EndoA gene encoding mouse cytokeratin and its methylation state in the CpG-rich region. Gene 104: 169–176, 1991

    Google Scholar 

  25. Riemer D, Dodemont H, Weber K: Analysis of the cDNA and gene encoding a cytoplasmic intermediate filament (IF) protein from the cephalochordate Branchistoma lanceolatum: Implications for the evolution of the IF protein family. Eur J Cell Biol 58: 128–135, 1992

    Google Scholar 

  26. Fuchs EV, Coppock SM, Green H, Cleveland DW: Two distinct classes of keratin genes and their evolutionary significance. Cell 27: 75–84, 1981

    Google Scholar 

  27. Waseem A, Gough AC, Spurr NK, Lane EB: Localization of the gene for human simple epithelial keratin 18 to chromosome 12 using polymerase chain reaction. Genomics 7: 188–194, 1990

    Google Scholar 

  28. Waseem A, Alexander CM, Steel JB, Lane EB: Embryonic simple epithelial keratins 8 and 18: Chromosomal location emphasizes difference from other keratin pairs. New Biologist 2: 464–478, 1990

    Google Scholar 

  29. Nadeau JH, Berger FG, Cox DG, Crosby JL, Davisson MT, Ferrara D, Fuchs E, Hart C, Hunihan L, Lalley PA, Langley SH, Martin GR, Nichols L, Phillips SJ, Roderick TH, Roop DR, Ruddle FH, Skow LC, Compton JG: A family of type I keratin genes and the homeo box-2 gene complex are closely linked to the rex locus on mouse chromosome 11. Genomics 5: 454–462, 1989

    Google Scholar 

  30. Rosenberg M, Fuchs E, Le Beau MM, Eddy RL, Shows TB: Three epidermal and one simple epithelial type II keratin gene map to human chromosome 12. Cytogenet Cell Genet 57: 33–38, 1991

    Google Scholar 

  31. Yoon SJ, Leblanc-Straceski J, Ward D, Krauter K, Kucherlapati R: Organization of the human keratin type II gene cluster at 12q13. Genomics 24: 502–508, 1994

    Google Scholar 

  32. Abe M, Oshima RG: A single human keratin 18 gene is expressed in diverse epithelial cells of transgenic mice. J Cell Biol 111: 1197–1206, 1990

    Google Scholar 

  33. Thorey IS, Meneses J, Neznanov N, Kulesh D, Pedersen R, Oshima RG: Embryonic expression of human keratin 18 and K18-beta-galactosidase fusion genes in transgenic mice. Dev Biol 160: 519–534, 1993

    Google Scholar 

  34. Oshima RG, Trevor K, Shevinsky LH, Ryder OA, Cecena G: Identification of the gene coding for the Endo B murine cytokeratin and its methylated, stable inactive state in mouse nonepithelial cells. Genes Dev 2: 505–516, 1988

    Google Scholar 

  35. Kulesh DA, Oshima RG: Cloning of the human keratin 18 gene and its expression in non-epithelial mouse cells. Mol Cell Biol 8: 267–272, 1988

    Google Scholar 

  36. Savtchenko ES, Freedberg IM, Choi I-Y, Blumenberg M: Inactivation of human keratin genes: The spectrum of mutations in the sequence of an acidic keratin pseudogene. Mol Biol Evol 5: 97–108, 1988

    Google Scholar 

  37. Ichinose Y, Morita T, Zhang F, Srimahasongcram S, Tondella MLC, Matsumoto M, Nozaki M, Matsushiro A: Nucleotide sequence and structure of the mouse cytokeratin endoB gene. Gene 70: 85–95, 1988

    Google Scholar 

  38. Vasseur M, Duprey P, Brulet P, Jacob F: One gene and one pseudogene for the cytokeratin Endo A. Proc Natl Acad Sci USA 82: 1155–1159, 1985

    Google Scholar 

  39. Baribault H, Oshima RG: Polarized and functional epithelia can form after the targeted inactivation of both mouse keratin 8 alleles. J Cell Biol 115: 1675–1684, 1991

    Google Scholar 

  40. Baribault H, Price J, Miyai K, Oshima RG: Mid-gestational lethality in mice lacking keratin 8. Genes Dev 7: 1191–1202, 1993

    Google Scholar 

  41. Andrews PW, Goodfellow PN, Damjanov I: Human teratocarcinoma cells in culture. Cancer Surv 2: 41–73, 1983

    Google Scholar 

  42. Damjanov I, Clark RK, Andrews PW: Expression of keratin polypeptides in human embryonal carcinoma cells. Intermediate Filaments 455: 732–733, 1985

    Google Scholar 

  43. Chisholm JC, Houliston E: Cytokeratin filament assembly in the preimplantation mouse embryo. Development 101: 565–582, 1987

    Google Scholar 

  44. Jackson BW, Grund C, Winter S, Franke WW, Illmense K: Formation of cytoskeletal elements during mouse embryogenesis: Epithelial differentiation and intermediate-sized filaments in early postimplantation embryos. Differentiation 20: 203–216, 1981

    Google Scholar 

  45. Duprey P, Morello D, Vasseur M, Babinet C, Condamine H, Brulet P, Jacob F: Expression of the cytokeratin endo A gene during early mouse embryogenesis. Proc Natl Acad Sci USA 82: 8538–8539, 1985

    Google Scholar 

  46. Oshima RG, Millan JL, Cecena G: Comparison of mouse and human keratin 18: A component of intermediate filaments expressed prior to implantation. Differentiation 33: 61–68, 1986

    Google Scholar 

  47. Ouellet T, Campron C, Lussier M, Lapointe L, Royal A: Differential regulation of keratin 8 and 18 messenger RNAs in differentiating F9 cells. Biochim Biophys Acta 1048: 194–201, 1990

    Google Scholar 

  48. Krauss S, Franke WW: Organization and sequence of the human gene encoding cytokeratin 8. Gene 86: 241–249, 1990

    Google Scholar 

  49. Strickland S, Mahdavi V: The induction of differentiation in teratocarcinoma stem cells by retinoic acid. Cell 15: 393–403, 1978

    Google Scholar 

  50. Silver LM, Martin GR, Strickland S: Teratocarcinoma stem cells. Cold Spring Harbor Conferences on Cell Proliferation p. 332, 1983

  51. Hogan BLM, Barlow DP, Tilly R: F9 teratocarcinoma cells as a model for the differentiation of parietal and visceral endoderm in the mouse embryo. Cancer Surv 2: 115–140, 1983

    Google Scholar 

  52. Hogan B, Costantini F, Lacy E: Manipulating the mouse embryo. p. 1, 1986

  53. Thorey IS, Cecena G, Reynolds W, Oshima RG: Alu sequence involvement in transcriptional insulation of the keratin 18 gene in transgenic mice. Mol Cell Biol 13: 6742–6751, 1993

    Google Scholar 

  54. Neznanov N, Thorey IS, Cecena G, Oshima RG: Transcriptional insulation of the human keratin 18 gene in transgenic mice. Mol Cell Biol 13: 2214–2223, 1993

    Google Scholar 

  55. Palmiter RD, Brinster RL: Germ-line transformation of mice. Ann Rev Genet 20: 465–499, 1986

    Google Scholar 

  56. Neznanov N, Kohwi-Shigematsu T, Oshima RG: Contrasting effects of the SATB1 core nuclear matrix attachment region and flanking sequences of the keratin 18 gene in transgenic mice. Mol Biol Cell 7: 541–552, 1996

    Google Scholar 

  57. Pankov T, Neznanov N, Umezawa A, Oshima RG: AP-1, ETS, and transcriptional silencers regulate retinoic acid-dependent induction of keratin 18 in embryonic cells. Mol Cell Biol 14: 7744–7757, 1994

    Google Scholar 

  58. Neznanov NS, Oshima RG: Cis regulation of the keratin 18 gene in transgenic mice. Mol Cell Biol 13: 1815–1823, 1993

    Google Scholar 

  59. Miyashita T, Yamamoto H, Takemoto Y, Nozaki M, Morita T, Matushiro A: Identification of differentiation-dependent DNase I-hypersensitive sites in the mouse Endo A gene. Gene 125: 151–158, 1993

    Google Scholar 

  60. Kulesh DA, Oshima RG: Complete structure of the gene for human keratin 18. Genomics 4: 339–346, 1989

    Google Scholar 

  61. Oshima RG, Abrams L, Kulesh D: Activation of an intron enhancer within the keratin 18 gene by expression of c-fos and c-jun in undifferentiated F9 embryonal carcinoma cells. Genes Dev 4: 835–848, 1990

    Google Scholar 

  62. Takemoto Y, Fujimura Y, Matsumoto M, Tamai Y, Morita T, Matsushiro A, Nozaki M: The promoter of the endo A cytokeratin gene is activated by a 3′ downstream enhancer. Nucl Acids Res 19: 2761–2765, 1991

    Google Scholar 

  63. Brulet P, Duprey, P, Vasseur M, Kaghad M, Morello D, Blanchet P, Babinet C, Condamine H: Molecular analysis of the first differentiations in the mouse embryo. Cold Spring Harb Symp Quant Biol 51–57, 1985

  64. Gunther M, Fre bourg T, Laithier M, Fossar N, Bouziane-Ouartini M, Lavialle C, Brison O: An Sp1 binding site and the minimal promoter contribute to overexpression of the cytokeratin 18 gene in tumorigenic clones relative to that in nontumorigenic clones of a human carcinoma cell line. Mol Cell Biol 15: 2490–2499, 1995

    Google Scholar 

  65. Rhodes K, Oshima RG: High level, tissue-specific expression of the keratin 18 gene by an alternative promoter in transgenic mice. (Submitted: 1996)

  66. Pankov R, Umezawa A, Maki R, Der CJ, Hauser CA, Oshima RG: Keratin 18 activation by Ha-ras is mediated through ETS and Jun binding sites. Proc Natl Acad Sci USA 91: 873–877, 1994

    Google Scholar 

  67. Yang-Yen HF, Chiu R, Karin M: Elevation of AP1 activity during F9 cell differentiation is due to increased c-jun transcription. New Biol 2: 351–361, 1990

    Google Scholar 

  68. Muller R, Wagner EF: Differentiation of F9 teratocarcinoma stem cells after transfer of c-fos proto-oncogenes. Nature 311: 438–442, 1984

    Google Scholar 

  69. Kwon M, Oshima RG: JunB does not inhibit the induction of c-Jun during the retinoic acid induced differentiation of F9 cells. Dev Dyn 193: 193–198, 1992

    Google Scholar 

  70. Hilberg F, Aguzzi A, Howells N, Wagner EF. c-Jun is essential for normal mouse development and hepatogenesis. Nature 365: 179–181, 1993

    Google Scholar 

  71. Lu B, Rothnagel JA, Longley MA, Tsai SY, Roop DR: Differentiation-specific expression of human keratin 1 is mediated by a composite AP-1/steroid hormone element. J Biol Chem 269: 7443–7449, 1994

    Google Scholar 

  72. Casatorres J, Navarro JM, Blessing M, Jorcano JL: Analysis of the control of expression and tissue specificity of the keratin 5 gene characteristics of basal keratinocytes. J Biol Chem 269: 20489–20469, 1994

    Google Scholar 

  73. Navarro JM, Casatorres J, Jorcano JL: Elements controlling the expression and induction of the skin hyperproliferation-associated keratin K6. J Biol Chem 270: 21362–21367, 1995

    Google Scholar 

  74. Bernerd F, Magnaldo T, Freedberg IM, Blumenberg M: Expression of the carcinoma-associated keratin K6 and the role of AP-1 proto-oncoproteins. Gene Expr 3: 187–199, 1993

    Google Scholar 

  75. Hu L, Gudas LJ: Activation of keratin 19 gene expression by a 3′ enhancer containing an AP1 site. J Biol Chem 269: 183–191, 1994

    Google Scholar 

  76. Hilberg F, Wagner EF: Embryonic stem (ES) cells lacking functional c-jun: Consequences for growth and differentiation, AP-1 activity and tumorigenicity. Oncogene 7: 2371–2380, 1992

    Google Scholar 

  77. Karim FD, Urness LD, Thummel CS, Klemsz MJ, McKercher SR, Celada A, VanBeveren C, Maki RA: The ETS domain: A new DNA binding motif that recognizes a purine-rich core DNa Sequence. Genes Dev 4: 1451–1453, 1990

    Google Scholar 

  78. Wasylyk B, Hahn SL, Giovane A: The ETS family of transcription factors. Eur J Biochem 211: 7–18, 1993

    Google Scholar 

  79. Kodandapani R, Pio F, Ni C-Z, Piccialli G, Klemsz M, McKercher S, Maki RA, Ely KR: A new pattern for helix-turn-helix recognition revealed by the PU.1 ETS-domain-DNA complex. Nature 380: 456–460, 1996

    Google Scholar 

  80. Henkel GW, McKercher SR, Yamamoto H, Anderson KL, Oshima RG, Maki RA: PU.1 but not Ets-2 is essential for macrophage development from ES cells. Blood 88: 2917–2926, 1996

    Google Scholar 

  81. Fujimura Y, Yamamoto H, Hamazato F, Nozaki M: One of two ETS-binding sites in the cytokeratin EndoA enhancer is essential for enhancer activity and binds to Ets-2 related proteins. Nucl Acids Res 22: 613–618, 1994

    Google Scholar 

  82. Hunter T: Cooperation between oncogenes. Cell 64: 249–270, 1991

    Google Scholar 

  83. Ruley HE: Transforming collaborations betweenras and nuclear oncogenes. Cancer Cells 2: 258–268, 1990

    Google Scholar 

  84. Bortner DM, Langer SJ, Ostrowski MC: Non-nuclear oncogenes and the regulation of gene expression in transformed cells. Crit Rev Oncog 4: 137–160, 1993

    Google Scholar 

  85. Karin M, Hunter T: Transcriptional control by protein phosphorylation: Signal transmission from the cell surface to the nucleus. Curr Biol 5: 747–757, 1995

    Google Scholar 

  86. Brunner D, Dückner K, Oellers N, Hafen E, Scholz H, Klämbt C: The ETS domain protein Pointed-P2 is a target of MAP kinase in the Sevenless signal transduction pathway. Nature 370: 386–389, 1994

    Google Scholar 

  87. Klambt C: The Drosophila gene pointed encodes two ETS-like proteins which are involved in the development of the midline glial cells. Development 117: 163–176, 1993

    Google Scholar 

  88. Yang B-S, Hauser CA, Henkel G, Colman MS, Van Beveren C, Stacey KJ, Hume DA, Maki RA, Ostrowski MC: Ras-mediated phosphorylation of a conserved threonine residue enhances the transactivation activity of c-Ets1 and c-Ets2. Mol Cell Biol 16: 538–547, 1996

    Google Scholar 

  89. Galang CK, Der CJ, Hauser CA: Oncogenic Ras can induce transcriptional activation through a variety of promoter elements, including tandem c-Ets-2 binding sites. Oncogene 9: 2913–2921, 1994

    Google Scholar 

  90. Galang CK, Garcia-Ramirez JJ, Solski PA, Der CJ, Neznanov NN, Oshima RG, Hauser CA: Oncogenic neu/ErbB-2 increases ETS, AP-1, and NF-kB-dependent gene expression, and inhibiting ETS activation blocks Neu-mediated cellular transformation. J Biol Chem 271: 7992–7998, 1996

    Google Scholar 

  91. Langer SJ, Bortner DM, Roussel MF, Sherr CJ, Ostrowski MC: Mitogenic signaling by colony-stimulating factor 1 and ras is suppressed by the ets-2 DNA-binding domain and restored by myc overexpression. Mol Cell Biol 12: 5355–5362, 1992

    Google Scholar 

  92. Sgouras DN, Athanasiou MA, Beal GJJr, Fisher RJ, Blair DG, Mavrothalassitis GJ: ERF: An ETS domain protein with strong transcriptional repressor activity, can suppressets associated tumorigenesis and is regulated by phosphorylation during cell cycle and mitogenic stimulation. EMBO J 14: 4781–4793, 1995

    Google Scholar 

  93. Giovane A, Pintzas A, Maira S-M, Sobeiszczuk P, Wasylyk B: Net, a newets transcription factor that is activated by Ras. Genes Dev 8: 1502–1513, 1994

    Google Scholar 

  94. Chiu R, Angeli P, Karin M: JunB differs in its biological properties from, and is a negative regulator of cJun. Cell 59: 979–986, 1989

    Google Scholar 

  95. Masquilier D, Sassone-Corsi P: Transcriptional cross-talk: Nuclear factors CREM and CREB bind to AP-1 sites and inhibit activation by jun. J Biol Chem 267: 22460–22466, 1992

    Google Scholar 

  96. Molina CA, Foulkes NS, Lalli E, Sassone-Corsi P: Inducibility and negative autoregulation of CREM: An alternative promoter directs the expression of ICER, an early response repressor. Cell 75: 875–886, 1993

    Google Scholar 

  97. De Cesare D, Vallone D, Caracciolo A, Sassone-Corsi P, Nerlov C, Verde P: Heterodimerization of c-Jun with ATF-2 and c-Fos is required for positive and negative regulation of the human urokinase enhancer. Oncogene 11: 365–376, 1995

    Google Scholar 

  98. Darmon M: Coexpression of specific acid and basic cytokeratins in teratocarcinoma-derived fibroblasts treated with 5-azacytidine. Dev Biol 110: 47–52, 1985

    Google Scholar 

  99. Semat A, Duprey P, Vasseur M, Darmon M: Mesenchymalepithelial conversions induced by 5-azacytidine: Appearance of cytokeratin endo-A messenger RNA. Differentiation 31: 61–66, 1986

    Google Scholar 

  100. Antequera F, Boyes J, Bird A: High levels of de novo methylation and altered chromatin structure at CpG islands in cell lines. Cell 62: 503–514, 1990

    Google Scholar 

  101. Mueller PR, Wold B:In vivo footprinting of a muscle specific enhancer by ligation mediated PCR. Science 246: 780–786, 1989

    Google Scholar 

  102. Pfeifer GP, Steigerwald SD, Mueller PR, Wold B, Riggs AD: Genomic sequencing and methylation analysis by ligation mediated PCR. Science 246: 810–813, 1989

    Google Scholar 

  103. Yamamoto H, Umezawa A, Rhodes K, Oshima RG: Tissue specific repression of the keratin 18 gene requires the methylation of an ETS site in the intron enhancer. (In preparation, 1996.)

  104. Nickel J, Short ML, Schmitz A, Eggert M, Renkawitz R: Methylation of the mouse M-lysozyme downstream enhancer inhibits heterotetrameric GABP binding. Nucl Acids Res 23: 4785–4792, 1995

    Google Scholar 

  105. Gaston K, Fried M: CpG methylation has differential effects on the binding of YY1 and ETS proteins to the bidirectional promoter of the surf-1 and surf-2 genes. Nucleic Acids Res 13: 901–909, 1995

    Google Scholar 

  106. Meehan RR, Lewis JD, Bird AP: Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA. Nucl Acids Res 20: 5085–5092, 1992

    Google Scholar 

  107. Nan X, Tate P, Li E, Bird A: DNA methylation specifies chromosomal localization of MeCP2. Mol Cell Biol 16: 414–421, 1995

    Google Scholar 

  108. Gottschling DE, Aparicio OM, Billington BL, Zakian VA: Position effect atS. cerevisiae telomeres: reversible repression of pol II transcription. Cell 63: 751–762, 1990

    Google Scholar 

  109. Renauld H, Aparicio OM, Zierath PD, Billington BL, Chablani SK, Gottschling DE: Silent domains are assembled continuously from the telomere and are defined by promoter distance and strength, and bySIR3 dosage. Genes Dev 7: 1133–1145, 1993

    Google Scholar 

  110. Rivier DH, RIne J: Silencing: The establishment and inheritance of stable, repressed transcription states. Curr Opin Genet Dev 2: 286–292, 1992

    Google Scholar 

  111. Laurenson P, Rine J: Silencers, silencing, and heritable transcriptional states. Microbiol Rev 56: 543–560, 1992

    Google Scholar 

  112. Shaffer CD, Wallrath LL, Elgin SCR: Regulating genes by packaging domains: Bits of heterochromatin in euchromatin? Trends Genet 9: 35–37, 1993

    Google Scholar 

  113. Csink AK, Henikoff S: Genetic modification of heterochromatic association and nuclear organization in Drosophila. Nature 381: 529–531, 1996

    Google Scholar 

  114. Heatley M, Maxwell P, Whiteside C, Toner P: Vimentin and cytokeratin expression in nodular hyperplasia and carcinoma of the prostate. J Clin Pathol 48: 1031–1034, 1995

    Google Scholar 

  115. Tabor JM, Oshima RG: Identification of mRNA species that code for extra-embryonic endodermal cytoskeletal proteins in differentiated derivatives of murine embryonal carcinoma cells. J Biol Chem 257: 8771–8774, 1982

    Google Scholar 

  116. Vasios G, Mader S, Gold J, Leid M, Lutz Y, Gaub M, Chambon P, Gudas L: The late retinoic acid induction of laminin B1 gene transcription involves RAR binding to the responsive element. EMBO J 10: 1149–1158, 1991

    Google Scholar 

  117. Vansant G, Reynolds WF: The consensus sequence of a major Alu subfamily contains a functional retinoic acid response element. Proc Natl Acad Sci USA 92: 8229–8233, 1995

    Google Scholar 

  118. Darmon M, Blumenberg M: Retinoic acid in epithelial and epidermal differentiation. In: Darmon M, Blumenberg M (eds) Molecular Biology of the Skin. Academic Press, San Diego, pp 181–206, 1993

    Google Scholar 

  119. Oshima RG, Howe WE, Klier FG, Adamson ED, Shevinsky LH: Intermediate filament protein synthesis in preimplantation murine embryos. Dev Biol 99: 447–455, 1983

    Google Scholar 

  120. Paulin D, Babinet C, Weber K, Osborn M: Antibodies as probes of cellular differentiations and cytoskeletal organization in the mouse blastocyst. Exp Cell Res 130: 297–304, 1980

    Google Scholar 

  121. Schwarz SM, Gallicano GI, McGaughey RW, Capco DG: A role for the intermediate filaments in the establishment of the primitive epithelia during mammalian embryogenesis. Mech Dev 53: 305–321, 1995

    Google Scholar 

  122. Lehtonen E: A monoclonal antibody against mouse oocyte cytoskeleton recognizing cytokeratin-type filaments. J Embryol Exp Morph 90: 197–209, 1985

    Google Scholar 

  123. Maruyama T, Umezawa A, Kusakari S, Kikuchi H, Nozaki M, Hata JI: Heat shock induces differentiation of human embryonal carcinoma cells into trophectoderm lineages. Exp Cell Res 224: 123–127, 1996

    Google Scholar 

  124. Moll R, Franke WW, Schiller DL, Geiger B, Krepler R: The catalog of human cytokeratins: Patterns of expression in normal epithelia, tumors and cultured cells. Cell 31: 11–24, 1982

    Google Scholar 

  125. Moll R, Levy R, Czernobilsky B, Hohlweg-Majert P, Dallenbach-Hellweg G, Franke WW: Cytokeratins of normal epithelia and some neoplasms of the female genital tract. Lab Invest 49: 599–610, 1983

    Google Scholar 

  126. Debus E, Moll R, Franke WW, Weber K, Osborn M: Immunohistochemical distinction of human carcinomas by cytokeratin typing with monoclonal antibodies. Am J Pathol 114: 121–130, 1984

    Google Scholar 

  127. Quinlan RA, Schiller DL, Hatzfeld M, Achstatter T, Moll R, Jorcano JL, Magin RM, Franke WW: Patterns of expression and organization of cytokeratin intermediate filaments. Ann NY Acad Sci 455: 282–306, 1985

    Google Scholar 

  128. Jahn L, Fouquet B, Rohe K, Franke WW: Cytokeratins in certain endothelial and smooth muscle cells of two taxonomically distant vertebrate species, Xenopus laevis and man. Differentiation 36: 234–254, 1987

    Google Scholar 

  129. Kuruc N, Franke WW: Transient coexpression of desmin and cytokeratins 8 and 18 in developing myocardial cells of some vertebrate species. Differentiation 38: 177–193, 1988

    Google Scholar 

  130. Owaribe K, Kartenbeck J, Rungger-Brandle E, Franke WW: Cytoskeletons of retinal pigment epithelial cells: Interspecies differences of expression patterns indicate independence of cell function from the specific complement of cytoskeletal proteins. Cell Tissue Res 254: 301–315, 1988

    Google Scholar 

  131. Taylor-Papadimitriou J, Stampfer M, Bartek J, Lewis A, Boshell M, Lane EB, Leigh IM: Keratin expression in human mammary epithelial cells cultured from normal and malignant tissue: Relation toin vivo phenotypes and influence of medium. J Cell Sci 94: 403–413, 1989

    Google Scholar 

  132. Dairkee SH, Puett L, Hackett AJ: Expression of basal and luminal epithelium-specific keratins in normal, benign, and malignant breast tissue. J Natl Cancer Inst 6: 691–695, 1988

    Google Scholar 

  133. Nagle RB, Bocker W, Davis JR, Heid HW, Kaufmann M, Lucas DO, Jarasch ED: Characterization of breast carcinomas by two monoclonal antibodies distinguishing myoepithelial from luminal epithelial cells. J Histochem 34: 869–881, 1986

    Google Scholar 

  134. Guelstein VI, Tchypysheva TA, Ermilova VD, Litvinova LV, Troyanosky SM, Bannikov GA: Monoclonal antibody mapping of keratins 8 and 17 and of vimentin in normal human mammary gland, benigh tumors, dysplasias and breast cancer. Int J Cancer 42: 147–153, 1988

    Google Scholar 

  135. Dairkee SH, Blayney-Moore CM, Smith HS, Hackett AJ: Concurrent expression of basal and luminal epithelial markers in cultures of normal human breast analyzed using monoclonal antibodies. Differentiation 32: 93–100, 1986

    Google Scholar 

  136. Trask DK, Band V, Zajchowski DA, Yaswen P, Suh T, Sager R: Keratins as markers that distinguish normal and tumor-derived mammary epithelial cells. Proc Natl Acad Sci USA 87: 2319–2323, 1990

    Google Scholar 

  137. Schonthal A, Srinivas S, Eckhart W: Induction of c-jun protooncogene expression and transcription factor AP-1 activity by the polyoma virus middle-sized tumor antigen. Proc Natl Acad Sci USA 89: 4972–4976, 1992

    Google Scholar 

  138. Ben-Levy R, Paterson HF, Marshall CF, Yarden Y: A single autophosphorylation site confers oncogenicity to the Neu/ErbB-2 receptor and enables coupling to the Map kinase pathway. EMBO J 13: 3302–3311, 1994

    Google Scholar 

  139. Schaafsma HE, Ramaekers FCS, van Muijen GNP, Lane EB, Leigh IM, Robben H, Huijsmans A, Ooms ECM: Distribution of cytokeratin polypeptides in human transitional cell carcinomas, with special emphasis on changing expression patterns during tumor progression. J Am J Pathol 136: 329–343, 1990

    Google Scholar 

  140. Moll R, Krepler R, Franke WW: Complex cytokeratin polypeptide patterns observed in certain human carcinomas. Differentiation 23: 256–269, 1983

    Google Scholar 

  141. Balaton AJ, Nehama-Sibony M, Gotheil C, Callard P, Baviera EE: Distinction between hepatocellular carcinoma, cholangiocarcinoma, and metastatic carcinoma based on immunohistochemical staining for carcinoembryonic antigen and for cytokeratin 19 on paraffin sections. J Pathol 156: 305–310, 1988

    Google Scholar 

  142. Johnson DE, Herdier BG, Medeiros LJ, Warnke RA, Rouse RV: The diagnostic utility of the keratin profiles of hepatocellular carcinoma and cholangiocarcinoma. Am J Surg Pathol 12: 187–197, 1988

    Google Scholar 

  143. Lai YS, Thung SN, Gerber MA, Chen ML, Schaffner F: Expression of cytokeratins in normal and diseased livers and in primary liver carcinomas. Arch Pathol Lab Med 113: 134–138, 1989

    Google Scholar 

  144. Schussler MH, Skoudy A, Ramaekers F, Real FX: Intermediate filaments as differentiation markers of normal pancreas and pancreas cancer. Am J Pathol 140: 559–568, 1992

    Google Scholar 

  145. Nagle RB, Brawer MK, Kittelson J, Clark V: Phenotypic relationships of prostatic intraepithelial neoplasia to invasive prostatic carcinoma. Am J Pathol 138: 119–128, 1991

    Google Scholar 

  146. Silen A, Wiklund B, Norlen BJ, Nilsson S: Evaluation of a new tumor marker for cytokeratin 8 and 18 fragments in healthy individuals and prostate cancer patients. The Prostate 24: 326–332, 1994

    Google Scholar 

  147. Dale BA, Holbrook KA: Developmental expression of human epidermal keratins and filaggrin. Curr Top Dev Biol 22: 127–151, 1987

    Google Scholar 

  148. Dale BA, Holbrook KA, Kimball JR, Hoff M, Sun TT: Expression of epidermal keratins and filaggrin during human fetal skin development. J Cell Biol 101: 1257–1269, 1985

    Google Scholar 

  149. Bader BL, Jahn L, Franke WW: Low level expression of cytokeratins 8, 18 and 19 in vascular smooth muscle cells of human umbilical cord and in cultured cells derived there-from, with an analysis of the chromosomal locus containing the cytokeratin 19 gene. Eur J Biochem 47: 300–319, 1988

    Google Scholar 

  150. Ferretti P, Fekete DM, Patterson M, Lane EB: Transient expression of simple epithelial keratins by mesenchymal cells of regenerating newt limb. Dev Biol 133: 415–424, 1989

    Google Scholar 

  151. Taylor-Papadimitriou J, Purkis P, Lane EB, McKay IA, Chang SE: Effects of SV40 transformation on the cytoskeleton and behavioural properties of human keratinocytes. Cell Diff 11: 169–180, 1982

    Google Scholar 

  152. Hronis TS, Steinberg ML, Defendi V, Sun T-T: Simple epithelial nature of some simian virus-40-transformed human epidermal keratinocytes. Cancer Res 44: 5797–5804, 1984

    Google Scholar 

  153. Morris A, Steinberg ML, Defendi V: Keratin gene expression in simian virus 40-transformed human keratinocytes. Proc Natl Acad Sci USA 82: 8498–8502, 1985

    Google Scholar 

  154. Bizub D, Wood AW, Skalka AM: Mutagenesis of the Ha-ras oncogene in mouse skin tumors induced by polycyclic aromatic hydrocarbons. Proc Natl Acad Sci USA 83: 6048–6052, 1986

    Google Scholar 

  155. Quintanilla M, Brown K, Ramsden M, Balmain A: Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis. Nature 322: 78–80, 1986

    Google Scholar 

  156. Balmain A, Ramsden M, Bowden GT, Smith J: Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas. Nature 307: 658–670, 1985

    Google Scholar 

  157. Aldaz CM, Trono D, Larcher F, Slaga TJ, Conti CJ: Sequential trisomization of chromosomes 6 and 7 in mouse skin premalignant lesions. Mol Carcinog 2: 22–26, 1989

    Google Scholar 

  158. Kemp CJ, Fee F, Balmain A: Allelotype analysis of mouse skin tumors using polymorphic microsatellites: Sequential genetic alterations on chromosomes 6, 7, and 11. Cancer Res 53: 6022–6027, 1993

    Google Scholar 

  159. Bremner R, Balmain A: Genetic changes in skin tumor progression: Correlation between presence of a mutant ras gene and loss of heterozygosity on mouse chromosome 7. Cell 61: 407–417, 1990

    Google Scholar 

  160. Buchmann A, Ruggeri B, Klein-Szanto AJ, Balmain A: Progression of squamous carcinoma cells to spindle carcinomas of mouse skin is associated with an imbalance of H-ras alleles on chromosome 7. Cancer Res 51: 4097–4101, 1991

    Google Scholar 

  161. Cheng C, Kilkenny A, Roop D, Yuspa S: The v-ras oncogene inhibits the expression of differentiation markers and facilitates expression of cytokeratins 8 and 18 in mouse keratinocytes. Mol Carcinog 3: 363–373, 1990

    Google Scholar 

  162. Yuspa SH, Vass W, Scolnick E: Altered growth and differentiation of cultured mouse epidermal cells infected with oncogenic retrovirus: Contrasting effects of viruses and chemicals. Cancer Res 43: 6021–6030, 1983

    Google Scholar 

  163. Yuspa SH, Kilkenny AE, Stanley J, Lichti U: Keratinocytes blocked in phorbol ester-responsive early stage of terminal differentiation by sarcoma viruses. Nature 314: 459–462, 1985

    Google Scholar 

  164. Roop DR, Huitfeldt H, Kilkenny A, Yuspa SH: Regulated expression of differentiation-associated keratins in cultured epidermal cells detected by monospecific antibodies to unique peptides of mouse epidermal keratins. Differentiation 35: 143–150, 1987

    Google Scholar 

  165. Diaz-Guerra M, Haddow S, Bauluz C, Jorócano J, Cano A, Balmain A, Quintanilla M: Expression of simple epithelial cytokeratins in mouse epidermal keratinocytes harboring harvey ras gene alterations. Cancer Res 52: 680–687, 1992

    Google Scholar 

  166. Cheng C, Tennenbaum T, Dempsey PJ, Coffey RJ, Yuspa SH, Dlugosz AA: Epidermal growth factor receptor ligands regulate keratin 8 expression in keratinocytes, and transforming growth factor alpha mediates the induction of keratin 8 by the v-ras-Ha oncogene. Cell Growth Differ 4: 317–327, 1993

    Google Scholar 

  167. Dlugosz AA, Cheng C, Williams EK, Darwiche N, Dempsey PJ, Mann B, Dunn AR, Coffey RJJr, Yuspa SH: Autocrine transforming growth factor alpha is dispensible for v-rasHa-induced epidermal neoplasia: potential involvement of alternate epidermal growth factor receptor ligands. Cancer Res 55: 1883–1893, 1995

    Google Scholar 

  168. Caulin C, Bauluz M, Gandarillas A, Cano A, Quintanilla M: Changes in keratin expression during malignant progression of transformed mouse epidermal keratinocytes. Exp Cell Res 204: 11–21, 1993

    Google Scholar 

  169. Larcher F, Bauluz C, Diaz-Guerra M, Quintanilla M, Conti CJ, Ballestin C, Jorcano JL: Aberrant expression of the simple epithelial type II keratin 8 by mouse skin carcinomas but not papillomas. Mol Carcinog 6: 112–121, 1992

    Google Scholar 

  170. Nischt R, Roop DR, Mehrel T, Yuspa SH, Rentrop M, Winter H, Schweizer J: Aberrant expression during two-stage mouse skin carcinogenesis of a type I-47 KDa keratin, K13, normally associated with terminal differentiation of internal stratified epithelia. Mol Carcinog 1: 96–108, 1988

    Google Scholar 

  171. Sutter C, Strickland JE, Welty DJ, Yuspa SH, Winter H, Schweizer J: v-Ha-ras-induced mouse skin papillomas exhibit aberrant expression of keratin K13 as do their 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate-induced analogues. Mol Carcinog 4: 467–476, 1991

    Google Scholar 

  172. Giminez-Conti I, Aldaz CM, Bianchi AB, Roop DR, Slaga TJ, Conti CJ: Early expression of type I K13 keratin in the progression of mouse skin papillomas. Carcinogenesis 11: 1995–1999, 1990

    Google Scholar 

  173. Bosch FX, Leube RE, Achtstatter T, Moll R, Franke WW: Expression of simple epithelial type cytokeratins in stratified epithelia as detected by immunolocalization and hybridizationin situ. J Cell Biol 106: 1635–1648, 1988

    Google Scholar 

  174. Markey AC, Lane EB, Churchill LJ, MacDonald DM, Leigh IM: Expression of simple epithelial keratins 8 and 18 in epidermal neoplasia. J Invest Dermatol 97: 763–770, 1991

    Google Scholar 

  175. Schaafsma HE, Van der Velden LA, Manni JJ, Peters H, Link M, Ruiter DJ, Ramaekers FCS: Increased expression of cytokeratins 8, 18 and vimentin in the invasion front of mucosal squamous cell carcinoma. J Pathol 170: 77–86, 1993

    Google Scholar 

  176. Saez E, Ruthberg SE, Mueller E, Oppenheim H, Smoluk J, Yuspa SH, Spiegelman BM: c-fos is required for malignant progression of skin tumors. Cell 82: 721–732, 1995

    Google Scholar 

  177. Hendrix MJC, Seftor EA, Chu YW, Seftor REB, Nagle RB, McDaniel KM, Leong SPL, Yohem KH: Coexpression of vimentin and keratins by human melanoma tumor cells: Correlation with invasive and metastatic potential. J Natl Cancer Inst 84: 165–174, 1992

    Google Scholar 

  178. Zarbo RJ, Gown AM, Nagle RB, Visscher DW, Crissman JD: Anomalous cytokeratin expression in malignant melanoma: One- and two-dimensional western blot analysis and immunohistochemical survey of 100 melanomas. Modern Pathol 3: 494–501, 1990

    Google Scholar 

  179. Lasota J, Hyjek E, Koo CH, Blonski J, Miettinen M: Cytokeratin-positive large-cell lymphomas of B-cell linage. Am J Surg Pathol 20: 346–354, 1996

    Google Scholar 

  180. Kulesh DA, Cecena G, Darmon YM, Vasseur M, Oshima RG: Post-translational regulation of keratins: Degradation of unpolymerized mouse and human keratins 18 and 8. Mol Cell Biol 9: 1553–1565, 1989

    Google Scholar 

  181. Kuruc N, Franke WW: Transient coexpression of desmin and cytokeratins 8 and 18 in developing myocardial cells of some vertebrate species. Differentiation 38: 177–193, 1988

    Google Scholar 

  182. Knapp AC, Franke WW: Spontaneous losses of control of cytokeratin gene expression in transformed, non-epithelial human cells occurring at different levels of regulation. Cell 59: 67–79, 1989

    Google Scholar 

  183. Walters MC, Magis W, Fiering S, Eidemiller J, Scalzo D, Groudine M, Martin DIK: Transcriptional enhancers act incis to suppress position-effect variegation. Genes Dev 10: 185–195, 1996

    Google Scholar 

  184. Dernburg AF, Broman KW, Fung JC, Marshall WF, Philips J, Agard DA, Sedat JW: Perturbation of nuclear architecture by long-distance chromosome interactions. Cell 85: 745–759, 1996

    Google Scholar 

  185. Lane EB, Alexander CM: Use of keratin antibodies in tumor diagnosis. Cancer Biol 1: 165–179, 1990

    Google Scholar 

  186. Moll R: Cytokeratins in the histological diagnosis of malignant tumors. Int J Biol Markers 9: 63–69, 1994

    Google Scholar 

  187. Weber K, Osborn M, Moll R, Wiklund B, Luning B: Tissue polypeptide antigen (TPA) is related to the non-epidermal keratin 8, 18 and 19 typical of simple and non-squamous epithelia: Re-evaluation of a human tumor marker. EMBO J 3: 2707–2714, 1984

    Google Scholar 

  188. Bonfrer JMG, Groeneveld EM, Korse CM, Van Dalen A, Oomen LCJM, Ivanyi D: Monoclonal antibody M3 used in tissue polypeptide-specific antigen assay for the quantification of tissue polypeptide antigen recognizes keratin 18. Tumor Biol 15: 210–222, 1994

    Google Scholar 

  189. Einarsson R: TPS—A cytokeratin marker for therapy control in breast cancer. Scan J Clin Lab Invest Suppl 221: 113–115, 1995

    Google Scholar 

  190. Baribault H, Penner J, Iozzo RV, Wilson-Heiner M: Colorectal hyperplasia and inflammation in keratin 8-deficient FVB/N mice. Genes Dev 8: 2964–2973, 1994

    Google Scholar 

  191. Baribault H, Wilson-Heiner M, Muller W, Penner J, Bakhiet N: Keratin 8 deficiency causes an earlier onset of mammary gland tumors in MMTV-polyoma middle T transgenic mice. Submitted, 1996

  192. Chu Y-W, Duffy JJ, Seftor REB, Nagle RB, Hendrix MJC: Transfection of a deleted CK18 cDNA into a highly metastatic melanoma cell line decreases the invasive potential. Clin Biotech 3: 27–33, 1991

    Google Scholar 

  193. Chu YW, Seftor EA, Romer LH, Hendrix MJC: Experimental coexpression of vimentin and keratin intermediate filaments in human melanoma cells augments motility. Am J Pathol 148: 63–69, 1996

    Google Scholar 

  194. Chu YW, Runyan RB, Oshima RG, Hendrix MJC: Expression of complete keratin filaments in mouse L cells augments cell migration and invasion. Proc Natl Acad Sci USA 90: 4261–4265, 1993

    Google Scholar 

  195. Robey HL, Hiscott PS, Grierson I: Cytokeratins and retinal epithelial cell behavior. J Cell Sci 102: 329–340, 1992

    Google Scholar 

  196. Klymkowsky MW, Miller RH, Lane EB: Morphology, behavior, and interaction of cultured epithelial cells after the antibody-induced disruption of keratin filament organization. J Cell Biol 96: 494–509, 1983

    Google Scholar 

  197. Thompson EW, Paik S, Brunner N, Sommers CL, Zugmaier G, Clarke R, Shima TB, Torri J, Donahue S, Lippman ME, Martin GR, Dickson RB: Association of increased basement membrane invasiveness with absence of estrogen receptor and expression of vimentin in human breast cancer cell lines. J Cell Physiol 150: 534–544, 1992

    Google Scholar 

  198. Bauman PA, Dalton WS, Anderson JM, Cress AE: Expression of cytokeratin confers multiple drug resistance. Proc Natl Acad Sci USA 91: 5311–5314, 1994

    Google Scholar 

  199. Anderson JM, Heindl LM, Bauman PA, Ludi CW, Dalton WS, Cress AE: Cytokeratin expression results in a drug-resistant phenotype to six different chemotherapeutic agents. Clin Cancer Res 2: 97–105, 1996

    Google Scholar 

  200. Parekh HK, Simpkins H: The differential expression of cytokeratin 18 in cisplatin-sensitive and-resistant human ovarian adenocarcinoma cells and its association with drug sensitivity. Cancer Res 55: 5203–5206, 1995

    Google Scholar 

  201. Frisch SM, Francis H: Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol 124: 619–626, 1994

    Google Scholar 

  202. Klymkowsky MW, Shook DR, Maynell L: Evidence that the deep keratinfilament systems of the Xenopus embryo act to ensure normal gastrulation. Proc Natl Acad Sci USA 89: 8736–8740, 1992

    Google Scholar 

  203. Torpey N, Wylie CC, Heasman J: Function of maternal cytokeratin in Xenopus development. Nature 357: 413–415, 1992

    Google Scholar 

  204. Brock J, McCluskey J, Baribault H, Martin P: Perfect wound healing in the keratin 8 deficient mouse embryo. Cell Motil Cytosk (in press)

  205. Dietrich WF, Lander ES, Smith JS, Moser AR, Gould KA, Luongo C, Borenstein N, Dove W: Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse. Cell 75: 631–639, 1993

    Google Scholar 

  206. Donald PJ, Cardiff RD, He D, Kendall K: Monoclonal antibody-porphyrin conjugate for head and neck cancer: The possible magic bullet. Otolaryngol Head Neck Surg 105: 781–787, 1991

    Google Scholar 

  207. Asch HL, Mayhew E, Lazo RO, Asch BB: Lipids covalently bound to keratins of mouse mammary epithelial cells. Biochem Mol Biol Int 29: 1161–1169, 1993

    Google Scholar 

  208. Hembrough TA, Vasudevan J, Allietta MM, Glass WFII, Gonias SL: A cytokeratin 8-like protein with plasminogen-binding activity is present on the external surfaces of hepatocytes, HepG2 cells and breast carcinoma cell lines. J Cell Sci 108: 1071–1082, 1995

    Google Scholar 

  209. Cadrin M, Marceau N, Baribault H: Griseofulvin hepatotoxicity-related effects in keratin 8 deficient FVB/N mice. Mol Biol Cell 6S: 2171, 1995

    Google Scholar 

  210. Ku N-O, Michie S, Soetikno R, Resurreccion E, Oshima RG, Omary MB: Susceptibility to hepatotoxicity in transgenic mice that express a dominant-negative human keratin 18 mutant. J Clin Invest, 1996

  211. Loranger A, Duclos S, Grenier A, Baribault H, Marceau N: Hampered liver recovery in keratin 8-deficient FVB/N mice after partial hepatectomy. Mol Biol Cell 6S: 2197, 1995

    Google Scholar 

  212. Ku N-O, Michie S, Oshima RG, Omary MB: Chronic hepatitis hepatocyte fragility, and increased soluble phosphoglycokeratins in transgenic mice expressing a keratin 18 conserved arginine mutant. J Cell Biol 131: 1303–1314, 1995

    Google Scholar 

  213. Coulombe PA, Hutton ME, Letai A, Hebert A, Paller AS, Fuchs E: Point mutations in human keratin 14 genes of epidermolysis bullosa simplex patients: Genetic and functional analysis. Cell 66: 1301–1311, 1991

    Google Scholar 

  214. Traub P, Shoeman RL: Intermediate filament proteins: Cytoskeletal elements with gene-regulatory functions? Int Rev Cytol 154: 1–103, 1994

    Google Scholar 

  215. Omary M, Baxter G, Chou C, Riopel C, Lin W, Strulovici B: PKCκ-related kinase associates with and phosphorylates cytokeratin 8 and 18. J Cell Biol 117: 583–593, 1994

    Google Scholar 

  216. Liao J, Lowthert LA, Ghori N, Omary MB: The 70-kDa heat shock proteins associate with glandular intermediate filaments in an ATP-dependent manner. J Biol Chem 270: 915–922, 1995

    Google Scholar 

  217. Liao J, Omary MB: 14–3–3 proteins associate with phosphorylated simple epithelial keratins during cell cycle progression and act as a solubility cofactor. J Cell Biol 133: 345–357, 1996

    Google Scholar 

  218. Stappenbeck TS, Lamb JA, Corcoran CM, Green KJ: Phosphorylation of the desmoplakin COOH terminus negatively regulates its interaction with keratin intermediate filament networks. J Biol Chem 269: 29351–29354, 1994

    Google Scholar 

  219. Stappenbeck TS, Green KJ: The desmoplakin carboxyl terminus coaligns with and specifically disrupts intermediate filament networks when expressed in cultured cells. J Cell Biol 116: 1197–1209, 1992

    Google Scholar 

  220. Godfroid E, Geuskens M, Dupressoir T, Parent I, Szpirer C: Cytokeratins are exposed on the outer surface of established human mammary carcinoma cells. J Cell Sci 99: 595–607, 1991

    Google Scholar 

  221. Riopel DL, Butt I, Omary B: Method of cell handling affects leakiness of cell surface labeling and detection of intracellular keratins. Cell Motil Cytoskel 26: 77–87, 1993

    Google Scholar 

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Oshima, R.G., Baribault, H. & Caulín, C. Oncogenic regulation and function of keratins 8 and 18. Cancer Metast Rev 15, 445–471 (1996). https://doi.org/10.1007/BF00054012

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