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Abstract

Volume 12, Issue 6 (November 2010) 12, 841–852; 10.1038/aja.2010.85

The role of TRPC6 in HGF-induced cell proliferation of human prostate cancer DU145 and PC3 cells

Yong Wang1, Dan Yue2, Kai Li3, Yi-Li Liu1, Chang-Shan Ren4 and Ping Wang1

1 Department of Urology, Fourth Affiliated Hospital, China Medical University, Shenyang 110032, China
2 College of Medical Laboratory Science, Tianjin Medical University, Tianjin 300070, China
3 Department of Surgical Oncology, First Affiliated Hospital, China Medical University, Shenyang 110001, China
4 Cancer Research Institute, First Affiliated Hospital, China Medical University, Shenyang 110001, China

Correspondence: Dr Ping Wang,cmu4h-wp@126.com

Received 31 January 2010; Revised 7 June 2010; Accepted 25 June 2010; Published online 13 September 2010.

Abstract

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 Ca2+ 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 Ca2+ entry. Furthermore, inhibition of TRPC6 channels arrested DU145 and PC3 cells at the G2/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.

Keywords: hepatocyte growth factor; human prostate cancer; proliferation; TRPC6

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