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Gender‐specific differences in the expression and activity of estrogen receptors alpha and beta in lung adenocarcinoma cells
Author(s) -
Mazhawidza Williard,
Dougherty Susan M,
Klinge Carolyn M
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a968
Subject(s) - estrogen receptor alpha , estrogen receptor beta , estrogen receptor , adenocarcinoma , estrogen , medicine , endocrinology , biology , lung cancer , cancer research , cell culture , coactivator , receptor , alpha (finance) , lung , transcription factor , cancer , breast cancer , gene , construct validity , nursing , patient satisfaction , biochemistry , genetics
Women have a higher incidence of lung adenocarcinoma than men. We evaluated estrogen receptor (ER) alpha and beta expression and activity in human lung adenocarcinoma cell lines, normal human bronchial epithelial cells (NHBE), and normal lung fibroblasts (NF1604). Higher levels of ERbeta than ERalpha protein were observed in all the lung cells. Estradiol (E2) stimulated proliferation only in cells from females and the antiestrogens 4‐hydroxytamoxifen (4‐OHT) and ICI 182,780 inhibited this response. Similarly, transcription of an ER reporter gene was stimulated by E2 in cells from females, but not males. Progesterone receptor (PR) was increased by E2 in 2 out of 5 cell lines from females, but none from males. E2 decreased E‐cadherin protein expression in some of the cell lines from females, as it did in MCF‐7 breast cancer cells, but not in the cells from males. Thus, ERalpha and ERbeta expression does not correlate with the effect of ER ligands on cellular activities in lung adenocarcinoma cells. There was no systematic difference in ERalpha or ERbeta intracellular location, determined by confocal microscopy, with gender. On average, expression of the ER coactivator DRIP205 was higher in cells from females versus males and higher in adenocarcinoma cells than NHBE. Although the mechanism for the difference in estrogenic responses with gender remains to be fully determined, these data suggest that ER antagonists may be useful in treating women with lung adenocarcinoma. Supported by grants from the Kentucky Lung Cancer Research program and the University of Louisville to CMK.