Androgens influence estrogen-induced responses in human breast carcinoma cells through cytochrome P450 aromatase
Androgens influence estrogen-induced responses in human breast carcinoma cells through cytochrome P450 aromatase
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DOI：
10.1023/a:1005782311558
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发表时间：
1997-05-01
影响因子：
3.8
通讯作者：
Brueggemeier, RW
中科院分区：
文献类型：
--
作者：
Burak, WE;Quinn, AL;Brueggemeier, RW
芳香酶细胞色素P450复合物负责雄激素向雌激素的体内转化。虽然乳腺癌上皮细胞已被报道具有可观的芳香化酶活性，其生物学意义仍然不确定。为了解决这个问题，雄激素对雌激素调节基因pS2在激素依赖的人乳腺癌细胞在体外的表达的影响进行了检查。类固醇剥夺MCF-7细胞暴露于不同浓度（1 nM，10 nM和100 nM）的雄烯二酮或睾酮2，4和6天。基线芳香酶活性为4.9（+/-3.1）fmol（H2O）-H-3/小时/μ g DNA [34.3（+/-21.3）fmol/小时/10（6）个细胞]，不受雄激素的影响。作为雌激素生物合成的指示，进行北方分析以定量pS2 mRNA表达。虽然在第2天没有观察到显著的pS2诱导，但暴露于100 nM睾酮的第4天和第6天均导致pS2 mRNA表达增加3倍。5 α-二氢睾酮（5 α-DHT）未能引起类似的pS2反应。用芳香酶抑制剂7 α（4 ′-氨基）苯硫基-1，4-雄甾二烯-3，17-二酮（7 α-APTADD）和10 μ M他莫昔芬抑制这种睾酮诱导的反应。MCF-7乳腺癌细胞具有足够高水平的内源性芳香酶活性，以将雄激素转化为雌激素并引起雌激素诱导的反应。芳香化酶的表达可能为凋亡反应细胞提供潜在的优势，提供了一个可以利用的额外的自分泌生长途径。
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 (H2O)-H-3/hour/mu g 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 mu M tamoxifen.MCF-7 breast cancer cells possess endogenous aromatase activity at high enough levels to convert androgens to estrogens and elicit an estrogen-induced response. The expression of aromatase may offer a potential advantage to hormone-responsive cells, providing an additional autocrine growth pathway which may be exploited.