Altered RECQ helicase expression in sporadic primary colorectal cancers

Victoria Valinluck Lao, Piri Welcsh, Yanxin Luo, Kelly T. Carter, Slavomir Dzieciatkowski, Suzanne Dintzis, Jane L Meza, Nora E Sarvetnick, Raymond J. Monnat, Lawrence A. Loeb, William M. Grady

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)458-469
Number of pages12
JournalTranslational Oncology
Volume6
Issue number4
DOIs
StatePublished - Aug 2013

Fingerprint

irinotecan
Colorectal Neoplasms
DNA Repair Enzymes
Messenger RNA
Topoisomerase I Inhibitors
Neoplasms
Colonic Neoplasms
DNA Damage
Immunohistochemistry
Drug Therapy
Cell Line
Enzymes
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Lao, V. V., Welcsh, P., Luo, Y., Carter, K. T., Dzieciatkowski, S., Dintzis, S., ... Grady, W. M. (2013). Altered RECQ helicase expression in sporadic primary colorectal cancers. Translational Oncology, 6(4), 458-469. https://doi.org/10.1593/tlo.13238

Altered RECQ helicase expression in sporadic primary colorectal cancers. / Lao, Victoria Valinluck; Welcsh, Piri; Luo, Yanxin; Carter, Kelly T.; Dzieciatkowski, Slavomir; Dintzis, Suzanne; Meza, Jane L; Sarvetnick, Nora E; Monnat, Raymond J.; Loeb, Lawrence A.; Grady, William M.

In: Translational Oncology, Vol. 6, No. 4, 08.2013, p. 458-469.

Research output: Contribution to journalArticle

Lao, VV, Welcsh, P, Luo, Y, Carter, KT, Dzieciatkowski, S, Dintzis, S, Meza, JL, Sarvetnick, NE, Monnat, RJ, Loeb, LA & Grady, WM 2013, 'Altered RECQ helicase expression in sporadic primary colorectal cancers', Translational Oncology, vol. 6, no. 4, pp. 458-469. https://doi.org/10.1593/tlo.13238
Lao VV, Welcsh P, Luo Y, Carter KT, Dzieciatkowski S, Dintzis S et al. Altered RECQ helicase expression in sporadic primary colorectal cancers. Translational Oncology. 2013 Aug;6(4):458-469. https://doi.org/10.1593/tlo.13238
Lao, Victoria Valinluck ; Welcsh, Piri ; Luo, Yanxin ; Carter, Kelly T. ; Dzieciatkowski, Slavomir ; Dintzis, Suzanne ; Meza, Jane L ; Sarvetnick, Nora E ; Monnat, Raymond J. ; Loeb, Lawrence A. ; Grady, William M. / Altered RECQ helicase expression in sporadic primary colorectal cancers. In: Translational Oncology. 2013 ; Vol. 6, No. 4. pp. 458-469.
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