Estrogen receptor α increases basal and cigarette smoke extract-induced expression of CYP1A1 and CYP1B1, but not GSTP1, in normal human bronchial epithelial cells

W. Han, B. T. Pentecost, R. L. Pietropaolo, M. J. Fasco, S. D. Spivack

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Gender-specific estrogen receptor α (ERα) expression may plausibly influence lung carcinogenesis in females. Initial genome-wide microarray studies confirmed that carcinogen metabolism genes (CYP1A1, CYP1B1) were those most responsive to cigarette smoke extract (CSE) in normal bronchial epithelial (NHBE) cells. These two genes encoding phase I bioactivating enzymes and the GSTP1 gene encoding a phase II deactivating enzyme were then tested for induction by ERα. NHBE cells (native ERα-) were transfected with wild-type ERα-adenoviral constructs, and then exposed to CSE, 17β-estradiol (E2), and/or the ERα inhibitor, ICI 182,780. The expression levels of CYP1A1, CYP1B1, and GSTP1 were then determined by RNA-specific quantitative RT-PCR and immunoassay. ERα increased the basal expression of CYP1B1 4.04-fold (P < 0.01) at the mRNA level and 6.5-fold at the protein level. ERα also increased the CSE-induced mRNA expression of CYP1B1 2.26-fold (P < 0.01), but not the protein expression. ERα did not alter the CYP1A1 mRNA levels, but did increase protein expression 2.0-fold (P < 0.01) on CSE exposure, and 6.2-fold (P < 0.01) upon E2 exposure. These effects could be inhibited by ICI 182,780. ERα did not alter the expression of GSTP1. Chromatin immunoprecipitation assay (Chip) assay confirmed ERα binding to CYP1B1 promoter near the transcription start site. These results suggest that ERα regulates the CYP1B1 expression at a transcriptional level, and CYP1A1 expression at a translational level. These data raise the possibility that inter-gender differences in expression of ERα that are known to exist in human lung may contribute to inter-individual expression differences in CYP1A1 and CYP1B1, and to differences in carcinogen metabolism and mutation.

Original languageEnglish (US)
Pages (from-to)202-211
Number of pages10
JournalMolecular Carcinogenesis
Volume44
Issue number3
DOIs
StatePublished - Nov 1 2005

Keywords

  • CYP1A1
  • CYP1B1
  • Cigarette smoke extract
  • Estrogen receptor
  • GSTP1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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