Aromatase overexpression enhances the stimulatory effects of adrenal androgens on MCF7 breast cancer cells.
The intratumoral conversion of adrenal androgens into estrogens by the aromatase enzyme complex may be an important mechanism of autocrine stimulation in hormone-dependent breast tumor. The effects of estrogens on tumor development are mediated by the activity of estrogen receptor alpha that induces gene expression and cell proliferation. Thus, estrogen biosynthesis 'in situ' and/or estrogen receptor action are the main targets of endocrine treatment in endocrine-dependent breast carcinoma. In the present study we demonstrate that three major adrenal androgens, dehydroepiandrosterone, 5-androstene-3beta, 17beta-diol and 4-androstene 3,17-dione, all acquire an estradiol-like biological efficacy in aromatase transfected MCF7 breast cancer cells. Our results suggest that in postmenopausal women aromatase inhibitors might be considered as an adjuvant approach to the treatment of hormone-dependent breast tumors that overexpress aromatase.
Maggiolini
Marcello
M
Department of Pharmaco-Biology, Facoltà di Farmacia, University of Calabria, I-87036 Rende, CS, Italy.
Bonofiglio
Daniela
D
Pezzi
Vincenzo
V
Carpino
Amalia
A
Marsico
Stefania
S
Rago
Vittoria
V
Vivacqua
Adele
A
Picard
Didier
D
Andò
Sebastiano
S
D000311:Adrenal Glands / Q000737:chemistry; D000728:Androgens / Q000494:pharmacology*; D015114:Androstenediol / Q000494:pharmacology; D000735:Androstenedione / Q000494:pharmacology; D001141:Aromatase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D000728:Androgens; D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D015114:Androstenediol; D001141:Aromatase