Contribution of aromatase to the deoxyribonucleic acid synthesis of MCF-7 human breast cancer cells and its suppression by aromatase inhibitors.
We have studied the effects of various steroids on DNA synthesis in MCF-7 human breast carcinoma cells, which have aromatase activity and which exert an oestrogen receptor-mediated growth, to assess the significance of intracellular aromatase on growth stimulation as well as inhibition by aromatase inhibitors. The cells were cultured for 96 h in phenol red-free medium containing 10% charcoal-treated fetal bovine serum and test reagents and pulse-labelled with [3H]thymidine. Physiological concentrations of oestradiol, oestrone, testosterone (T) and androstenedione (AD) stimulated thymidine incorporation. However, oestrone-sulphate and dihydrotestosterone (DHT) only stimulated at concentrations greater than the physiological levels. T and DHT stimulation was blocked by tamoxifen, but not by cyproterone acetate, suggesting that the stimulation was mediated via the oestrogen receptor but not by the androgen receptor. Stimulation by T and AD was reduced by aminoglutethimide and 14 alpha-hydroxy-4-androstene-3,6,17-trione, both of which inhibit aromatase activity, however, stimulation by nonaromatizable DHT was not reduced by the inhibitors, suggesting that androgens were converted by the intracellular aromatase to oestrogens which stimulated the thymidine incorporation. It is suggested that intracellular aromatase significantly contributes to the stimulation of DNA synthesis and that aromatase inhibitors suppress the stimulation.
Kitawaki
J
J
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Japan.
Fukuoka
M
M
Yamamoto
T
T
Honjo
H
H
Okada
H
H
D000728:Androgens / Q000494:pharmacology; D001141:Aromatase / Q000502:physiology*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D003534:Cyproterone / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004967:Estrogens / Q000494:pharmacology; D006801:Humans; D011960:Receptors, Estrogen / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014867:Water / Q000378:metabolism
D000728:Androgens; D047072:Aromatase Inhibitors; D004273:DNA, Neoplasm; D004967:Estrogens; D011960:Receptors, Estrogen; D014867:Water; D013629:Tamoxifen; D003534:Cyproterone; D001141:Aromatase