The direct proliferative stimulus of dehydroepiandrosterone on MCF7 breast cancer cells is potentiated by overexpression of aromatase.
In women after menopause aromatization of adrenal androgens represents the main source of estrogens, which may promote the development of hormone-dependent breast tumor. Several studies have attempted to determine the cell type within carcinomas that is responsible for 'in situ' estrogen biosynthesis and whether the amount produced may sustain relevant biological effects. Here we show P450arom mRNA and protein expression together with immunocytochemical localization of aromatase in the epithelial MCF7 breast cancer cell line. Moreover, we demonstrate that the enhanced aromatization of dehydroepiandrosterone in aromatase transfected MCF7 cells confers biological advantages such as proliferative stimulation similar to that induced by estradiol. Our results suggest that aromatase inhibitors may be particularly effective in the treatment of hormone-dependent breast cancer disease in postmenopausal women.
Maggiolini
M
M
Department of Pharmaco-Biology, University of Calabria, I-87036 Rende CS, Italy.
Carpino
A
A
Bonofiglio
D
D
Pezzi
V
V
Rago
V
V
Marsico
S
S
Picard
D
D
Andò
S
S
D001141:Aromatase / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003687:Dehydroepiandrosterone / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D004958:Estradiol / Q000096:biosynthesis / Q000378:metabolism; D047628:Estrogen Receptor alpha; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D003687:Dehydroepiandrosterone; D004958:Estradiol; D001141:Aromatase