Regulation of endogenous gene expression in human non-small cell lung cancer cells by estrogen receptor ligands

Pamela A. Hershberger, A. Cecilia Vasquez, Beatriz Kanterewicz, Stephanie Land, Jill M. Siegfried, Mark Nichols

Research output: Contribution to journalArticlepeer-review

138 Scopus citations

Abstract

Estrogen receptor (ER) agonists and antagonists elicit distinct responses in non-small cell lung cancer (NSCLC) cells. To determine how such responses are generated, the expression of ERα, ERβ, and ER coregulators in human lung fibroblasts and human NSCLC cell lines was evaluated by immunoblot. Ligand-dependent estrogenic responses in NSCLC cells are probably generated via ERβ and the p160 coactivator GRIP1/ TIF2, because expression of these proteins was detected, but not full-length ERα or the p160 coactivator SRC-1. ERβ and GRIP1/TIF2 are shown to interact in vitro in a ligand-dependent manner and thus may form functional transcription complexes in NSCLC cells. Furthermore, the capacity of ER ligands to regulate gene expression in NSCLC cells was explored using gene miniarrays. Expression profiles were examined after treatment with ER agonist 17-β-estradiol (E2), the pure ER antagonist ICI 182,780 (fulvestrant, Faslodex), or epidermal growth factor, which served as a positive control for an alternative growth stimulus. E-cadherin and inhibitor of differentiation 2 were differentially regulated by E2 versus ICI 182,780 in 201T and 273T NSCLC cell lines. Epidermal growth factor also stimulated proliferation of these cells but had no effect on expression of E-cadherin and inhibitor of differentiation 2, suggesting they are specific targets of ER signaling. These data show that NSCLC cells respond to estrogens/antiestrogens by altering endogenous gene expression and support a model in which ICI 182,780 reduces proliferation of NSCLC cells via its ability to disrupt ER signaling. ICI 182,780 may therefore have therapeutic benefit in NSCLC.

Original languageEnglish (US)
Pages (from-to)1598-1605
Number of pages8
JournalCancer Research
Volume65
Issue number4
DOIs
StatePublished - Feb 15 2005

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