SRC-3 is required for prostate cancer cell proliferation and survival
SRC-3 is required for prostate cancer cell proliferation and survival
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DOI：
10.1158/0008-5472.can-04-4076
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发表时间：
2005-09-01
期刊：
影响因子：
11.2
通讯作者：
Tsai, NJ
中科院分区：
文献类型：
--
作者：
Zhou, HJ;Yan, J;Tsai, NJ
前列腺癌是美国男性最常见的癌症。目前，类固醇受体共激活剂已被提议有时以不依赖类固醇的方式介导前列腺癌的发生和进展。类固醇受体辅激活因子-3（SRC-3、p/CIP、AIB1、ACTR、RAC3 和 TRAM-1）是核激素受体（包括雄激素受体）共激活因子 p160 家族的成员。 SRC-3 在许多癌症中经常扩增或过度表达。然而，SRC-3 在癌细胞增殖和存活中的作用仍知之甚少。在这项研究中，我们发现SRC-3在前列腺癌患者中过度表达，其过度表达与前列腺癌增殖相关，与细胞凋亡呈负相关。与患者数据一致，我们观察到小干扰RNA降低SRC-3表达会降低不同前列腺癌细胞系的增殖、延迟G(1)-S转变并增加细胞凋亡。此外，随着SRC-3表达的减少，增殖细胞核抗原和Bcl-2的表达以及前列腺癌细胞中溴脱氧尿苷的掺入也减少。最后，在前列腺癌细胞中敲低SRC-3并诱导短发夹RNA表达可减少裸鼠肿瘤生长。总而言之，这些发现表明 SRC-3 是前列腺癌增殖和存活的重要调节因子。
Prostate cancer is the most common cancer in men in America. Currently, steroid receptor coactivators have been proposed to mediate the development and progression of prostate cancer, at times in a steroid-independent manner. Steroid receptor coactivator-3 (SRC-3, p/CIP, AIB1, ACTR, RAC3, and TRAM-1) is a member of the p160 family of coactivators for nuclear hormone receptors including the androgen receptor. SRC-3 is frequently amplified or overexpressed in a number of cancers. However, the role of SRC-3 in cancer cell proliferation and survival is still poorly understood. In this study, we show that SRC-3 is overexpressed in prostate cancer patients and its overexpression correlates with prostate cancer proliferation and is inversely correlated with apoptosis. Consistent with patient data, we have observed that reduction of SRC-3 expression by small interfering RNA decreases proliferation, delays the G(1)-S transition, and increases cell apoptosis of different prostate cancer cell lines. Furthermore, with decreased SRC-3 expression, proliferating cell nuclear antigen and Bcl-2 expression, as well as bromodeoxyuridine incorporation in prostate cancer cells are reduced. Finally, knockdown of SRC-3 with inducible short hairpin RNA expression in prostate cancer cells decreased tumor growth in nude mice. Taken together, these findings indicate that SRC-3 is an important regulator of prostate cancer proliferation and survival.