ISSN:
1573-7217
Schlagwort(e):
androgens
;
aromatase
;
biosynthesis
;
breast
;
estrogen
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Abstract The aromatase cytochrome P450 complex is responsible forthe in vivo conversion of androgens to estrogens.Although breast cancer epithelial cells have been reportedto have appreciable aromatase activity, its biologic significanceremains uncertain. To address this, the effect ofandrogens on the expression of the estrogen-regulated genepS2 in hormone-dependent human breast carcinoma cells invitro was examined.Steroid-deprived MCF-7 cells were exposed to varying concentrations(1 nM, 10 nM, and 100 nM ofandrostenedione or testosterone for 2, 4, and 6days. Baseline aromatase activity was 4.9 (± 3.1)fmol 3H2O/hour/μg DNA [34.3 (± 21.3) fmol/hr/106 cells]and was not influenced by the androgens. Asan indication of estrogen biosynthesis, northern analysis wasperformed to quantitate pS2 mRNA expression. Although nosignificant pS2 induction was observed at 2 days,both 4 and 6 day exposure to 100nM testosterone resulted in a 3-fold increase inpS2 mRNA expression. 5α-dihydrotestosterone (5α-DHT) failed to elicita similar pS2 response. This testosterone-induced response wasinhibited with the aromatase inhibitor 7α(4′DV-amino) phenylthio-1,4-androstadiene-3,17-dione (7α-APTADD)and with 10 μM tamoxifen.MCF-7 breast cancer cells possess endogenous aromatase activityat high enough levels to convert androgens toestrogens and elicit an estrogen-induced response. The expressionof aromatase may offer a potential advantage tohormone-responsive cells, providing an additional autocrine growth pathwaywhich may be exploited.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1023/A:1005782311558
Permalink
