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Carcinogenesis Advance Access published online on September 24, 2007
Carcinogenesis, 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, T. Blomquist1, D. N. Mullins, Y. Yoon, D. R. Hernandez, M. Al-Bagdhadi, J. Ruiz, J. Hammersley and J. C. Willey2

Departments of Medicine and Pathology, University of Toledo, Toledo, Ohio, 43614, /USA

2 Author to whom proofs are to be addressed: J.C. Willey, 419 383-3541, 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 upregulated 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 upregulation of ERCC5. CEBPG, E2F1, and YY1 binding to their respective sites was confirmed by EMSA. 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 data presented here, it is reasonable to hypothesize that they may contribute to risk for bronchogenic carcinoma.

Key Words: CEBPG • ERCC5 • XPG • E2F1 • DNA repair

1 These first-authors contributed equally

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


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