ABSTRACT
The antiandrogen flutamide (FLU) has been reported to exert antiproliferative action on both male and postmenopausal breast cancer and to inhibit growth of chemically induced rat breast cancer. We studied the effects of various concentrations of FLU on the growth of the ER+, AR+ and PR+ MCF-7 and the ER-, AR- and PR- MDA-MB-231 human breast cancer cell lines. The growth of MCF-7 cells in both steroid free and estradiol supplemented media was inhibited by FLU. MDA-MB-231 cell growth was not affected by FLU. Our data show a direct inhibitory action of FLU on human breast cancer cells and suggest a different susceptibility to the antiproliferative action of FLU, which seems to be related to the steroid receptor status.
ABSTRACT
Dehydroepiandrosterone and 5-en-Androstene-3beta, 17beta-diol affect MCF-7 human breast cancer cell growth through estrogen receptor, as shown by Tamoxifen counteraction. To assess whether the aromatization of these adrenal androgens to classical estrogens is required to stimulate proliferation, we evaluated the aromatase activity of MCF-7 cells. Aromatase activity was determined in both whole cells grown as monolayer cultures and microsomal fraction of cell homogenates. The conversion of Androstendione to Estrone was very low in cell cultures. By contrast, a high aromatase activity was found in cell homogenates, indicating that in isolated microsomal fractions of MCF-7 cells aromatase is unveiled. Since in whole cultured MCF-7 cells the conversion of androgens to estrogens is negligible, we suggest that the stimulatory effect of DHEA and ADIOL on the 'in vitro' growth of MCF-7 does not involve the aromatase pathway.
