Altered RECQ Helicase Expression in Sporadic Primary Colorectal Cancers |
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Authors: | Victoria Valinluck Lao Piri Welcsh Yanxin Luo Kelly T Carter Slavomir Dzieciatkowski Suzanne Dintzis Jane Meza Nora E Sarvetnick Raymond J Monnat Lawrence A Loeb William M Grady |
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Institution: | 2. Department of Surgery, University of Washington Medical School, Seattle, WA;3. Department of Surgery, University of Nebraska Medical School, Omaha, NE;4. Genetics Division, Department of Medicine, University of Washington Medical School, Seattle, WA;5. Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University Medical School, Guangzhou, China;11. Division of Gastroenterology, Department of Medicine, University of Washington Medical School, Seattle, WA |
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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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