Involvement of arginine methyltransferase CARMI in androgen receptor function and prostate cancer cell viability
Involvement of arginine methyltransferase CARMI in androgen receptor function and prostate cancer cell viability
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DOI：
10.1002/pros.20438
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发表时间：
2006-09-01
期刊：
影响因子：
2.8
通讯作者：
Whang, Young E.
中科院分区：
文献类型：
--
作者：
Majumder, Samarpan;Liu, Yuanbo;Whang, Young E.
背景雄激素受体（AR）可能在前列腺癌进展中发挥作用。辅激活子相关精氨酸甲基转移酶（CARM 1）催化组蛋白H3在Arg-17位的甲基化。对原发性前列腺癌标本进行CARM 1的免疫组织化学。通过染色质免疫沉淀分析CARM 1募集和组蛋白甲基化。评估了CARM 1过表达或CARM 1敲低对报告基因测定、细胞增殖、凋亡和内源性雄激素靶基因表达的影响。CARM 1表达在去势抵抗的前列腺癌细胞核中增加，但在雄激素刺激的前列腺癌细胞核中没有增加。雄激素刺激导致CARM 1募集和雄激素应答增强子处组蛋白H3的甲基化。CARM 1的过表达刺激和CARM 1敲低抑制AR报告基因活性。CARM 1敲低抑制细胞增殖并诱导细胞凋亡。CARM 1基因敲低可抑制雄激素依赖性前列腺特异性抗原（PSA）和hK 2 mRNA的表达。CARM 1对AR功能至关重要，可能在前列腺癌进展中发挥作用。CARM 1可能代表前列腺癌的新治疗靶点。
BACKGROUND. Androgen receptor (AR) may play a role in prostate cancer progression. Coactivator-associated arginine methyltransferase (CARM1) catalyzes methylation of histone H3 at Arg-17.METHODS. Immunohistochemistry of CARM1 was performed on primary prostate cancer specimens. CARM1 recruitment and histone methylation was analyzed by chromatin immunoprecipitation. The effect of CARM1 overexpression or CARM1 knockdown was assessed on reporter assays, cell proliferation, apoptosis, and endogenous androgen target gene expression.RESULTS. CARM1 expression was increased in the nucleus of castration-resistant, but not androgen-stimulated prostate cancer. Androgen stimulation led to CARM1 recruitment and methylation of histone H3 at androgen responsive enhancers. Overexpression of CARM1 stimulated and CARM1 knockdown inhibited AR reporter activity. CARM1 knockdown inhibited cell proliferation and induced apoptosis. CARM1 knockdown inhibited androgen-dependent prostate specific antigen (PSA) and hK2 mRNA expression.CONCLUSIONS. CARM1 is essential for AR function and may play a role in prostate cancer progression. CARM1 may represent a novel therapeutic target in prostate cancer.