CEBPG transcription factor correlates with antioxidant and DNA repair genes in normal bronchial epithelial cells but not in individuals with bronchogenic carcinomaReport as inadecuate




CEBPG transcription factor correlates with antioxidant and DNA repair genes in normal bronchial epithelial cells but not in individuals with bronchogenic carcinoma - Download this document for free, or read online. Document in PDF available to download.

BMC Cancer

, 5:141

First Online: 29 October 2005Received: 07 July 2005Accepted: 29 October 2005DOI: 10.1186-1471-2407-5-141

Cite this article as: Mullins, D.N., Crawford, E.L., Khuder, S.A. et al. BMC Cancer 2005 5: 141. doi:10.1186-1471-2407-5-141

Abstract

BackgroundCigarette smoking is the primary cause of bronchogenic carcinoma BC, yet only 10–15% of heavy smokers develop BC and it is likely that this variation in risk is, in part, genetically determined. We previously reported a set of antioxidant genes for which transcript abundance was lower in normal bronchial epithelial cells NBEC of BC individuals compared to non-BC individuals. In unpublished studies of the same NBEC samples, transcript abundance values for several DNA repair genes were correlated with these antioxidant genes. From these data, we hypothesized that antioxidant and DNA repair genes are co-regulated by one or more transcription factors and that inter-individual variation in expression and-or function of one or more of these transcription factors is responsible for inter-individual variation in risk for BC.

MethodsThe putative transcription factor recognition sites common to six of the antioxidant genes were identified through in silico DNA sequence analysis. The transcript abundance values of these transcription factors n = 6 and an expanded group of antioxidant and DNA repair genes n = 16 were measured simultaneously by quantitative PCR in NBEC of 24 non-BC and 25 BC individuals.

ResultsCEBPG transcription factor was significantly p < 0.01 correlated with eight of the antioxidant or DNA repair genes in non-BC individuals but not in BC individuals. In BC individuals the correlation with CEBPG was significantly p < 0.01 lower than that of non-BC individuals for four of the genes XRCC1, ERCC5, GSTP1, and SOD1 and the difference was nearly significant for GPX1. The only other transcription factor correlated with any of these five target genes in non-BC individuals was E2F1. E2F1 was correlated with GSTP1 among non-BC individuals, but in contrast to CEBPG, there was no significant difference in this correlation in non-BC individuals compared to BC individuals.

ConclusionWe conclude that CEBPG is the transcription factor primarily responsible for regulating transcription of key antioxidant and DNA repair genes in non-BC individuals. Further, we conclude that the heavy smokers selected for development of BC are those who have sub-optimal regulation of antioxidant and DNA repair genes by CEBPG.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-5-141 contains supplementary material, which is available to authorized users.

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Author: D-Anna N Mullins - Erin L Crawford - Sadik A Khuder - Dawn-Alita Hernandez - Youngsook Yoon - James C Willey

Source: https://link.springer.com/







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