CYP17A1 and Androgen-Receptor Expression in Prostate Carcinoma Tissues and Cancer Cell Lines.
CYP17A1 and Androgen-Receptor Expression in Prostate Carcinoma Tissues and Cancer Cell Lines.
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DOI：
10.1159/000499276
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发表时间：
2019-11-01
期刊：
影响因子：
1.6
通讯作者：
Koukourakis, Michael I
中科院分区：
文献类型：
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作者：
Giatromanolaki, Alexandra;Fasoulaki, Virginia;Koukourakis, Michael I
背景：CYP17A1参与脱氢表雄酮和雄烯二酮的类固醇合成。目的：探讨细胞色素PYP17A1在前列腺癌生长中的作用。材料和方法：检测前列腺癌标本和前列腺癌细胞系中细胞色素PYP17A1和雄激素受体(AR)的表达。结果：CYP17A1在前列腺癌细胞胞浆中呈强阳性表达(中位数为50%的癌细胞，范围为0-100%)。癌细胞中AR的核表达与细胞色素P17A1直接相关(p<；0.0001，r=0.51)。与PC3和DU145细胞株相比，激素依赖的22Rv1细胞株表达细胞色素P17A1和AR蛋白和基因(p<；0.0001)。睾酮和地塞米松可诱导AR的核表达，这种作用可被阿比特龙阻断。睾酮孵育不影响细胞色素P17A1的表达，而阿比特龙则显著降低其表达。阿比特龙抑制睾酮刺激的22Rv1细胞的生长和迁移。结论：大约一半的人前列腺癌中有CYP17A1的强表达，这意味着癌细胞可以在细胞内合成雄激素。阿比特龙有效地阻断了AR的核积聚，抑制了细胞色素P17A1的表达。CYP17A1可作为选择最佳激素抗癌治疗方案的生物标志物。
BACKGROUND: CYP17A1 is involved in the steroidogenesis of dehydroepiandrosterone and androstenedione. CYP17A is a target for the hormonal treatment of prostate cancer (PCa).OBJECTIVES: To investigate the role of CYP17A1 as a driver of PCa growth.MATERIALS AND METHODS: We examined the expression of CYP17A1 and of androgen receptors (AR) in PCa specimens and in PCa cell lines.RESULTS: CYP17A1 was strongly expressed in the cytoplasm of PCa cells (median 50% of cancer cells, range 0-100%). The nuclear AR expression in cancer cells was directly related with CYP17A1 (p < 0.0001, r = 0.51). The hormone dependent 22Rv1 cell line expressed the CYP17A1 and AR protein and mRNA, in contrast to the PC3 and DU145 cell lines (p < 0.0001). Testosterone and dexamethasone induced nuclear expression of AR and this effect was abolished by abiraterone. CYP17A1 levels were not affected by the incubation with testosterone, while abiraterone significantly reduced its expression. Abiraterone reduced the growth rate and migration of testosterone stimulated 22Rv1 cells.CONCLUSIONS: CYP17A1 is strongly expressed in half about of human prostate carcinomas, implying an intracellular androgen synthesis by cancer cells. Abiraterone effectively blocked nuclear accumulation of AR and suppressed CYP17A1 expression. CYP17A1 may function as a biomarker to select the best hormonal anticancer therapy.