title: [Essential role of TRPC6 in the proliferation of gastric cancer and its mechanism].
abstract: OBJECTIVE
  To investigate the essential role and mechanism of TRPC6 gene in the development of gastric cancer.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  In the preclinical models tested, TRPC6 channels are essential for gastric cancer development via regulation of G(2)/M phase transition.
authors.affiliation: Department of Chemoradiotherapy, Ruijin Hospital, Shanghai Jiaotong University Medical College, Shanghai 200025, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Cai
authors.forename: Gang
authors.initials: G
authors.lastname: Ren
authors.forename: Xia
authors.initials: X
authors.lastname: Ding
authors.forename: Yi-zheng
authors.initials: YZ
authors.lastname: Wang
authors.forename: Ye-ning
authors.initials: YN
authors.lastname: Jin
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016203:CDC2 Protein Kinase; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019926:Cyclin B / Q000378:metabolism; D018844:Cyclin-Dependent Kinases; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D050052:TRPC Cation Channels / Q000378:metabolism*; D000074287:TRPC6 Cation Channel; D014162:Transfection; D047368:Tumor Burden
chemical_list: D019926:Cyclin B; D011994:Recombinant Proteins; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases