[Growth inhibition of MCF-7 human breast cancer cells by aromatase inhibitors].
MCF-7 cell line is a model for estrogen-dependent tumors that have both aromatase activity and estrogen receptor. We studied the contribution of aromatase to cell growth and DNA synthesis by means of aromatase inhibitors. MCF-7 cells were cultured in phenol red-free medium containing 10% charcoal-treated fetal bovine serum and test reagents for 96 hours and pulse-labeled with [3H]thymidine for 1 hour. Physiological concentrations of estradiol, estrone, testosterone(T) and androstenedione(delta 4A) increased [3H] thymidine incorporation. Stimulation by T or dihydrotestosterone (DHT) was reduced by tamoxifen, but not by androgen receptor blocker cyproterone acetate, suggesting that T and DHT stimulated cellular proliferation via estrogen receptor but not via androgen receptor. Stimulation by T or delta 4A was reduced by aromatase inhibitors (aminoglutethimide and 14 alpha-hydroxy-4-androstene-3,6,17-trione), but stimulation by nonaromatizable DHT was not reduced by aromatase inhibitors. These results have suggested that estrogens which are biosynthesized from androgens by the intracellular aromatase play a significant role in growth stimulation of MCF-7 cells and that aromatase inhibitors block this pathway. These methods are useful in assessing the ability of aromatase inhibitors to suppress cell growth.
Fukuoka
M
M
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine.
Kitawaki
J
J
Yamamoto
T
T
Okada
H
H
D000616:Aminoglutethimide / Q000494:pharmacology*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D003534:Cyproterone / Q000031:analogs & derivatives / Q000494:pharmacology; D017373:Cyproterone Acetate; D005260:Female; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry / Q000473:pathology*; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D047072:Aromatase Inhibitors; D011960:Receptors, Estrogen; D013629:Tamoxifen; D000616:Aminoglutethimide; D017373:Cyproterone Acetate; D003534:Cyproterone