PMID: 9164678May 1, 1997Paper

Androgens influence estrogen-induced responses in human breast carcinoma cells through cytochrome P450 aromatase

Breast Cancer Research and Treatment
W E BurakRobert W Brueggemeier

Abstract

The aromatase cytochrome P450 complex is responsible for the in vivo conversion of androgens to estrogens. Although breast cancer epithelial cells have been reported to have appreciable aromatase activity, its biologic significance remains uncertain. To address this, the effect of androgens on the expression of the estrogen-regulated gene pS2 in hormone-dependent human breast carcinoma cells in vitro was examined. Steroid-deprived MCF-7 cells were exposed to varying concentrations (1 nM, 10 nM, and 100 nM of androstenedione or testosterone for 2,4, and 6 days. Baseline aromatase activity was 4.9 (+/-3.1) fmol 3H2O/hour/microgram DNA [34.3 (+/-21.3) fmol/hr/10(6) cells] and was not influenced by the androgens. As an indication of estrogen biosynthesis, northern analysis was performed to quantitate pS2 mRNA expression. Although no significant pS2 induction was observed at 2 days, both 4 and 6 day exposure to 100 nM testosterone resulted in a 3-fold increase in pS2 mRNA expression. 5 alpha-dihydrotestosterone (5 alpha-DHT) failed to elicit a similar pS2 response. This testosterone-induced response was inhibited with the aromatase inhibitor 7 alpha (4'-amino) phenylthio-1,4-androstadiene-3,17-dione (7 alpha-APTADD) and with 10 micr...Continue Reading

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