Referenced in: none

Automatically associated channels: TRP , TRPC , TRPC6

Title: [Essential role of TRPC6 in the proliferation of gastric cancer and its mechanism].

Authors: Rong Cai, Gang Ren, Xia Ding, Yi-Zheng Wang, Ye-ning Jin

Journal, date & volume: Zhonghua Zhong Liu Za Zhi, 2012 Aug , 34, 577-81

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23158989

Abstract
To investigate the essential role and mechanism of TRPC6 gene in the development of gastric cancer.The expression of TRPC6 protein was assessed in gastric cancer tissues and normal tissues adjacent to the cancer from 30 patients with gastric cancer. The inhibiting effect of TRPC6 activity on cell growth, cell cycle of a human gastric cancer cell line AGS cells, tumor progression and development of xenografted human gastric cancer in a mouse model was tested using dominant-negative mutant TRPC6 (DNC6). The survival of mice bearing xenografted tumors in the GFP and DNC6 was compared using Kaplan-Meier analysis. All statistical tests were two-sided.The TRPC6 protein in the tumor tissues and para-tumor tissues was (21.60 ± 8.32)% versus (7.14 ± 2.24)%. After transfection of DNC6 virus for 24 hours, 48 hours, 72 hours and 96 hours, the growth inhibition rates of gastric cancer cells were (36.90 ± 1.13)%, (44.06 ± 2.17)%, (52.12 ± 2.76)% and (50.89 ± 1.97)%, respectively. The clone formation rates of control group and DNC6 group were (14.70 ± 3.00)% versus (43.80 ± 7.00)%. After transfection with DNC6 virus for 0, 24, 36 and 48 hours, the G(2)/M phase arrest was (20.34 ± 1.98)%, (24.31 ± 2.37)%, (27.70 ± 2.36)%, (35.10 ± 3.0)% in the DNC6 group and (18.40 ± 2.01)%, (18.0% ± 1.72)%, (17.50 ± 1.74)%, (16.80 ± 1.71)% in the control group, respectively. Inhibition of TRPC6 activity also reduced the subcutaneous tumor volume in the mouse models with xenografted human tumors (P < 0.05).In the preclinical models tested, TRPC6 channels are essential for gastric cancer development via regulation of G(2)/M phase transition.