Elsevier

Translational Oncology

Volume 6, Issue 4, August 2013, Pages 458-469, IN7-IN10
Translational Oncology

Altered RECQ Helicase Expression in Sporadic Primary Colorectal Cancers1,2

https://doi.org/10.1593/tlo.13238Get rights and content
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open access

Abstract

Deregulation of DNA repair enzymes occurs in cancers and may create a susceptibility to chemotherapy. Expression levels of DNA repair enzymes have been shown to predict the responsiveness of cancers to certain chemotherapeutic agents. The RECQ helicases repair damaged DNA including damage caused by topoisomerase I inhibitors, such as irinotecan. Altered expression levels of these enzymes in colorectal cancer (CRC) may influence the response of the cancers to irinotecan. Thus, we assessed RECQ helicase (WRN, BLM, RECQL, RECQL4, and RECQL5) expression in primary CRCs, matched normal colon, and CRC cell lines. We found that BLM and RECQL4 mRNA levels are significantly increased in CRC (P = .0011 and P < .0001, respectively), whereas RECQL and RECQL5 are significantly decreased (P = .0103 and P = .0029, respectively). RECQ helicase expression patterns varied between specific molecular subtypes of CRCs. The mRNA and protein expression of the majority of the RECQ helicases was closely correlated, suggesting that altered mRNA expression is the predominant mechanism for deregulated RECQ helicase expression. Immunohistochemistry localized the RECQ helicases to the nucleus. RECQ helicase expression is altered in CRC, suggesting that RECQ helicase expression has potential to identify CRCs that are susceptible to specific chemotherapeutic agents.

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1

Support for these studies was provided by the National Institutes of Health (NIH; RO1CA115513, P30CA15704, UO1CA152756, U54CA143862, and P01CA077852; W.M.G.), Burroughs Wellcome Fund Translational Research Award for Clinician Scientist (W.M.G.), ACS Fellowship PF-11-086-01-TBG (V.V.L.), 2T32DK007742-16 (V.V.L.), American Society of Colon and Rectal Surgeons, General Surgery Resident Research Initiation Grant (V.V.L.), and NIH National Cancer Institute F32CA1591555- 01 (V.V.L.). The authors declare no conflict of interest.

2

This article refers to supplementary materials, which are designated by Tables W1 to W5 and Figures W1 to W3 and are available online at http://www.transonc.com.