Gender difference in the activity but not expression of estrogen receptors alpha and beta in human lung adenocarcinoma cells.
The higher frequency of lung adenocarcinoma in women smokers than in men smokers suggests a role for gender-dependent factors in the etiology of lung cancer. We evaluated estrogen receptor (ER) alpha and beta expression and activity in human lung adenocarcinoma cell lines and normal lung fibroblasts. Full-length ERalpha and ERbeta proteins were expressed in all cell lines with higher ERbeta than ERalpha. Although estradiol (E(2)) binding was similar, E(2) stimulated proliferation only in cells from females, and this response was inhibited by anti-estrogens 4-hydroxytamoxifen (4-OHT) and ICI 182,780. In contrast, E(2) did not stimulate replication of lung adenocarcinoma cells from males and 4-OHT or ICI did not block cell proliferation. Similarly, transcription of an estrogen response element-driven reporter gene was stimulated by E(2) in lung adenocarcinoma cells from females, but not males. Progesterone receptor (PR) expression was increased by E(2) in two out of five adenocarcinoma cell lines from females, but none from males. E(2) 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 cell lines from males. Thus, ERalpha and ERbeta expression does not correlate with the effect of ER ligands on cellular activities in lung adenocarcinoma cells. On the other hand, coactivator DRIP205 expression was higher in lung adenocarcinoma cells from females versus males and higher in adenocarcinoma cells than in normal human bronchial epithelial cells. DRIP205 and other ER coregulators may contribute to differences in estrogen responsiveness between lung adenocarcinoma cells in females and males.
Dougherty
Susan M
SM
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Mazhawidza
Williard
W
Bohn
Aimee R
AR
Robinson
Krista A
KA
Mattingly
Kathleen A
KA
Blankenship
Kristy A
KA
Huff
Mary O
MO
McGregor
William G
WG
Klinge
Carolyn M
CM
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D056913:Mediator Complex Subunit 1; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D020218:Response Elements; D012723:Sex; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D015820:Cadherins; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C538855:MED1 protein, human; D056913:Mediator Complex Subunit 1; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D014157:Transcription Factors; D004958:Estradiol