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Title: Blockade of TRPC6 channels induced G2/M phase arrest and suppressed growth in human gastric cancer cells
Author: Cai, Rong ; Ding, Xia ; Zhou, Kechun ; Shi, Yu ; Ge, Ruiliang ; Ren, Gang ; Jin, Yening ; null(王以政)
Source: INTERNATIONAL JOURNAL OF CANCER
Issued Date: 2009
Volume: 125, Issue:10, Pages:2281-2287
Keyword: TRPC6 ; gastric cancer ; cell cycle ; RECEPTOR POTENTIAL CHANNELS ; PROLIFERATION ; CA2+ ; CHECKPOINTS ; ACTIVATION ; EXPRESSION ; ENTRY
Subject: Oncology
Corresponding Author: Wang, YZ (reprint author), Chinese Acad Sci, Inst Neurosci, SIBS, Lab Neural Signal Transduct, 320 Yueyang Rd, Shanghai 200031, Peoples R China,
English Abstract: Channels formed by file canonical transient receptor potential (TRPC) subfamily of proteins are Ca(2+)-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 Ca(2+) 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 Ca(2+) elevation regulated by TRPC6 channels is essential for G2/M phase transition and for the development of gastric cancers. (C) 2009 UICC
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1629
Appears in Collections:神经所(总)_期刊论文
神经信号转导研究组_期刊论文

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Cai, Rong; Ding, Xia; Zhou, Kechun; Shi, Yu; Ge, Ruiliang; Ren, Gang; Jin, Yening; Wang, Yizheng.Blockade of TRPC6 channels induced G2/M phase arrest and suppressed growth in human gastric cancer cells,INTERNATIONAL JOURNAL OF CANCER,2009,125(10):2281-2287
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