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Carcinogenesis Advance Access originally published online on September 24, 2007
Carcinogenesis 2007 28(12):2552-2559; doi:10.1093/carcin/bgm214
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

CEBPG regulates ERCC5/XPG expression in human bronchial epithelial cells and this regulation is modified by E2F1/YY1 interactions

E.L. Crawford1,2,{dagger}, T. Blomquist1,2,{dagger}, D.N. Mullins1,2, Y. Yoon1, D.R. Hernandez1, M. Al-Bagdhadi1, J. Ruiz1, J. Hammersley1 and J.C. Willey1,2,*

1 Department of Medicine
2 Department of Pathology, The University of Toledo, Toledo, OH 43614, USA

* To whom correspondence should be addressed. Tel: +1 419 383 3541; Fax: +1 419 383-6244;Email: james.willey2{at}utoledo.edu

Marked inter-individual variation in lung cancer risk cannot be accounted for solely by cigarette smoke and other environmental exposures. Evidence suggests that variation in bronchial epithelial cell expression of key DNA repair genes plays a role. Variation in these genes correlates with variation in expression of CEBPG and E2F1 transcription factors. Here, we investigated the mechanistic basis for correlation of the DNA repair gene ERCC5 (previously known as XPG) with CEBPG and E2F1. CEBPG expression vector transfected into H23 or H460 cell lines up-regulated endogenous ERCC5 and also luciferase from a reporter construct containing 589 bp of ERCC5 5' regulatory region. A recognition site for CEBPG and a region containing sites for YY1 on the sense strand and E2F1 on the anti-sense strand participated in CEBPG up-regulation of ERCC5. CEBPG, E2F1 and YY1 binding to their respective sites were confirmed by electrophoretic mobility shift assay. Thus, we conclude that CEBPG regulates ERCC5 expression and this regulation is modified by E2F1/YY1 interactions. Several polymorphisms have been identified in these regions and, based on the data presented here, it is reasonable to hypothesize that they may contribute to risk for bronchogenic carcinoma.

Abbreviations: ACTB, β-actin; BC, bronchogenic carcinoma; BEC, bronchial epithelial cell; IS, internal standard; mRNA, messenger RNA; NE, nuclear extract; NT, native template; P-1, promoter-1; P-3, promoter-3; PCR, polymerase chain reaction; SMIS, standardized mixture of internal standard; StaRT–PCR, Standardized reverse transcription–polymerase chain reaction

{dagger} These authors contributed equally to this work.

Received August 3, 2007; revised September 12, 2007; accepted September 15, 2007.


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