Activity and intracellular location of estrogen receptors alpha and beta in human bronchial epithelial cells.
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 approximately twice as much ERbeta as ERalpha. ERalpha and ERbeta 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 ERalpha-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.
Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Margarita M
MM
Ivanova
Williard
W
Mazhawidza
Susan M
SM
Dougherty
John D
JD
Minna
Carolyn M
CM
Klinge
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000032:analysis / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000032:analysis / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D006915:Hydroxytestosterones / Q000494:pharmacology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D012737:Sex Factors
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006915:Hydroxytestosterones; C032278:4,17 beta-dihydroxy-4-androstene-3-one; D004958:Estradiol