Department of Urology, Fourth Affiliated Hospital, China Medical University, Shenyang 110032, China.
Asian J Androl. 2010 Nov;12(6):841-52. doi: 10.1038/aja.2010.85. Epub 2010 Sep 13.
Hepatocyte growth factor (HGF) is a glycoprotein that induces prostate cancer cell proliferation, migration and invasion. The activation of transient receptor potential canonical 6 (TRPC6) channels is considered important in promoting prostate cancer cell proliferation. In this study, we assessed the role of endogenous TRPC6 channels in the HGF-induced cell proliferation of prostate cancer. Reverse transcription-PCR and Western blotting were used to investigate TRPC6 expression. Electrophysiological techniques (whole-cell patch clamp configuration) and Ca(2+) imaging analysis were used to investigate the channel activity in cells. The effects of TRPC6 channels on cell cycle progression, cell apoptosis and cell growth were also examined. TRPC6 and c-MET were expressed in DU145 and PC3 cells. In addition, functional TRPC6 channels were present in DU145 and PC3 cells, and TRPC6 knockdown suppressed TRPC-like currents evoked by oleoyl-2-acetyl-sn-glycerol (OAG). Inhibition of TRPC6 channels in DU145 and PC3 cells abolished OAG- and HGF-induced Ca(2+) entry. Furthermore, inhibition of TRPC6 channels arrested DU145 and PC3 cells at the G(2)/M phase and suppressed HGF-induced cell proliferation. Collectively, our results indicate that TRPC6 has an important role in HGF-induced DU145 and PC3 cell proliferation.
肝细胞生长因子（HGF）是一种糖蛋白，可诱导前列腺癌细胞增殖、迁移和侵袭。瞬时受体电位经典型 6 通道（TRPC6）的激活被认为在促进前列腺癌细胞增殖中很重要。在这项研究中，我们评估了内源性 TRPC6 通道在 HGF 诱导的前列腺癌细胞增殖中的作用。采用逆转录-PCR 和 Western blot 分析来研究 TRPC6 的表达。采用电生理技术（全细胞膜片钳构型）和 Ca(2+)成像分析来研究细胞中的通道活性。还研究了 TRPC6 通道对细胞周期进程、细胞凋亡和细胞生长的影响。TRPC6 和 c-MET 在 DU145 和 PC3 细胞中表达。此外，功能性 TRPC6 通道存在于 DU145 和 PC3 细胞中，并且 TRPC6 敲低抑制了油酰基-2-乙酰基-sn-甘油（OAG）诱导的 TRPC 样电流。在 DU145 和 PC3 细胞中抑制 TRPC6 通道消除了 OAG 和 HGF 诱导的 Ca(2+)内流。此外，抑制 TRPC6 通道使 DU145 和 PC3 细胞停滞在 G(2)/M 期，并抑制了 HGF 诱导的细胞增殖。总之，我们的结果表明，TRPC6 在 HGF 诱导的 DU145 和 PC3 细胞增殖中起重要作用。
