Activity and intracellular location of estrogen receptors α and β in human bronchial epithelial cells

Margarita M. Ivanova, Williard Mazhawidza, Susan M. Dougherty, John D. Minna, Carolyn M. Klinge

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Gender differences in lung disease and cancer are well-established. We reported estrogenic transcriptional responses in lung adenocarcinoma cells from females but not males despite similar estrogen receptor (ER) expression. Here we tested the hypothesis that normal human bronchial epithelial cells (HBECs) show gender-independent estrogenic responses. We report that a small sample of HBECs express ∼twice as much ERβ as ERα. ERα and ERβ were located in the cytoplasm, nucleus, and mitochondria. In contrast to lung adenocarcinoma cells, estradiol (E2) induced estrogen response element (ERE)-mediated luciferase reporter activity in transiently transfected HBECs regardless of donor gender. Overexpression of ERα-VP16 increased ERE-mediated transcriptional activity in all HBECs. E2 increased and 4-hydroxytamoxifen and ICI 182,780 inhibited HBEC proliferation and cyclin D1 expression in a cell line-specific manner. In conclusion, the response of HBECs to ER ligands is gender-independent suggesting that estrogenic sensitivity may be acquired during lung carcinogenesis.

Original languageEnglish (US)
Pages (from-to)12-21
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume305
Issue number1-2
DOIs
Publication statusPublished - Jun 16 2009

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Keywords

  • Cyclin D1
  • Estrogen receptor
  • Lung adenocarcinoma (human)
  • Normal lung (human)
  • SMRT

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry

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