Jun activation domain-binding protein 1 expression in oral squamous cell carcinomas inversely correlates with the cell cycle inhibitor p27

Med Oncol. 2012 Dec;29(4):2499-504. doi: 10.1007/s12032-012-0177-0. Epub 2012 Feb 4.

Abstract

The Jun activation domain-binding protein 1 (Jab1) may be involved in degradation of the cyclin-dependent kinase inhibitor p27, but it has not been clarified. In this study, we observed expression levels of Jab1 and p27 in oral squamous cell carcinoma (OSCC) and normal oral mucosa tissue and evaluated whether the Jab1 expression is correlated with p27 protein levels and how it is clinically relevant OSCC. The clinicopathological features and immunohistochemical expression levels of Jab1 and p27 proteins were immunohistochemically studied in 206 specimens from patients who underwent surgical resection for OSCC. Survival analyses were performed by using the Kaplan-Meier method. Jab1 overexpression was detected in 83% (171 of 206) of OSCCs and 19% (4 of 21) of normal oral mucosa. While p27 expression was 60% in OSCCs. We found an inverse correlation between Jab1 and p27 expression levels (P<0.001). Kaplan-Meier survival analysis showed that Jab1 overexpression and p27 low expression were significantly associated with poor prognosis of patients. Our findings suggest that Jab1 expression is inversely correlated with p27 expression levels, suggesting that Jab1 overexpression contributes to pathogenesis of OSCC by degradating p27 expression. Furthermore, control of Jab1 could be a novel target of therapy in OSCCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • COP9 Signalosome Complex
  • Carcinoma, Squamous Cell / chemistry*
  • Carcinoma, Squamous Cell / etiology
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Cyclin-Dependent Kinase Inhibitor p27 / analysis*
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Enzyme Activation
  • Female
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / analysis*
  • Intracellular Signaling Peptides and Proteins / physiology
  • Male
  • Middle Aged
  • Mouth Mucosa / chemistry
  • Mouth Neoplasms / chemistry*
  • Mouth Neoplasms / etiology
  • Mouth Neoplasms / mortality
  • Mouth Neoplasms / pathology
  • Peptide Hydrolases / analysis*
  • Peptide Hydrolases / physiology
  • Prognosis

Substances

  • CDKN1B protein, human
  • Intracellular Signaling Peptides and Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Peptide Hydrolases
  • COPS5 protein, human
  • COP9 Signalosome Complex