Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 125, Issue 10, Pages 2281-2287Publisher
WILEY-BLACKWELL
DOI: 10.1002/ijc.24551
Keywords
TRPC6; gastric cancer; cell cycle
Categories
Funding
- National Natural Science Foundation of China [200603806600]
Ask authors/readers for more resources
Channels formed by file canonical transient receptor potential (TRPC) subfamily of proteins are Ca2+-permeable, nonselective cation channels with various functions. Through I phospholipase C (PLO-dependent mechanism TRPC6, a member of TRPC subfamily. can be activated by receptor tyrosine kinases (RTK) or G protein-coupled receptors (GPCR),. which are implicated in cell proliferation and human malignancies. Here, we report that TRPC6 has a critical role in human gastric cancer development. Expression of TRPC6 Was greatly upregulated in human gastric cancer epithelial cells compared with that in normal gastric epithelial cells. Treatment of AGS or MKN45 cells, human gastric cancer cell lines, with SKF96365, an agent known to inhibit TRPC channels. arrested cell cycle in G2/M phase and suppressed cell growth. Importantly, expressing a dominant negative mutant of TRPC6 (DNC6) in these cells also arrested cell cycle in G2/M phase all inhibited cell growth. The Ca2+ elevation in the MKN45 cells evoked by histamine war, inhibited by SKF96365 and DNC6. Moreover, inhibition of TRPC6 suppressed the formation of gastric tumors in nude mice. These results suggest that Ca2+ elevation regulated by TRPC6 channels is essential for G2/M phase transition and for the development of gastric cancers. (C) 2009 UICC
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available