ARFGAP3, an androgen target gene, promotes prostate cancer cell proliferation and migration
ARFGAP3, an androgen target gene, promotes prostate cancer cell proliferation and migration
复制标题
DOI：
10.1002/ijc.26224
复制
发表时间：
2012-05
影响因子：
6.4
通讯作者：
D. Obinata;Ken-ichi Takayama;T. Urano;T. Murata;K. Ikeda;Kuniko Horie-Inoue;Y. Ouchi;Satoru Takahashi;S. Inoue
中科院分区：
文献类型：
--
作者：
D. Obinata;Ken-ichi Takayama;T. Urano;T. Murata;K. Ikeda;Kuniko Horie-Inoue;Y. Ouchi;Satoru Takahashi;S. Inoue
ADP核糖基化因子GTP酶激活蛋白3（ARFGAP 3）是一种与高尔基体相关并调节囊泡运输途径的GTP酶激活蛋白。在本研究中，我们研究了ARFGAP 3对前列腺癌细胞生物学的贡献。我们发现，在雄激素敏感的LNCaP细胞中，100 nM双氢睾酮（DHT）在mRNA和蛋白质水平上诱导ARFGAP 3表达。我们用FLAG标记的ARFGAP 3或对照空载体产生了LNCaP细胞的稳定转染子，并表明与对照细胞相比，ARFGAP 3过表达促进了细胞增殖和迁移。我们发现ARFGAP 3与桩蛋白（paxillin）相互作用，桩蛋白是一种对细胞移动和迁移很重要的粘着斑适配蛋白。小干扰RNA（siRNA）介导的ARFGAP 3敲低显示ARFGAP 3 siRNA显著降低LNCaP细胞生长。如LNCaP细胞中的荧光素酶测定所示，外源性ARFGAP 3和桩蛋白表达协同促进前列腺特异性抗原（PSA）增强子上的雄激素受体（AR）依赖性反式激活活性。因此，我们的研究结果表明，ARFGAP 3是一种新的雄激素调节基因，可以与桩蛋白协同促进前列腺癌细胞增殖和迁移。
ADP ribosylation factor GTPase‐activating protein 3 (ARFGAP3) is a GTPase‐activating protein that associates with the Golgi apparatus and regulates the vesicular trafficking pathway. In the present study, we examined the contribution of ARFGAP3 to prostate cancer cell biology. We showed that ARFGAP3 expression was induced by 100 nM of dihydrotestosterone (DHT) at both the mRNA and protein levels in androgen‐sensitive LNCaP cells. We generated stable transfectants of LNCaP cells with FLAG‐tagged ARFGAP3 or a control empty vector and showed that ARFGAP3 overexpression promoted cell proliferation and migration compared with control cells. We found that ARFGAP3 interacted with paxillin, a focal adhesion adaptor protein that is important for cell mobility and migration. Small interfering RNA (siRNA)‐mediated knockdown of ARFGAP3 showed that ARFGAP3 siRNA markedly reduced LNCaP cell growth. Androgen receptor (AR)‐dependent transactivation activity on prostate‐specific antigen (PSA) enhancer was synergistically promoted by exogenous ARFGAP3 and paxillin expression, as shown by luciferase assay in LNCaP cells. Thus, our results suggest that ARFGAP3 is a novel androgen‐regulated gene that can promote prostate cancer cell proliferation and migration in collaboration with paxillin.