TGF-β-induced cell-cycle arrest through the p21waf1/cip1_G1 cyclin/CDKS-p130 pathway in gastric-carcinoma cells

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Title
TGF-β-induced cell-cycle arrest through the p21waf1/cip1_G1 cyclin/CDKS-p130 pathway in gastric-carcinoma cells
Author(s)
Y D Yoo; Ju Youn Choi; Su Jae Lee; Jun S Kim; Byung Re Min; Young Ik Lee; Yoon Koo Kang
Bibliographic Citation
International Journal of Cancer, vol. 83, no. 4, pp. 512-517
Publication Year
1999
Abstract
Transforming growth factor-β1 (TGF-β) inhibits cell-cycle progression of many types of cells by arresting them in G1/S phase through inhibition of the active cyclin-Cdk complexes that lead to inhibition of Rb phosphorylation. In gastric-cancer cells, SNU16, TGF-β treatment induced enhanced expression of p21(WAF1/CIP1) (p21), which inhibited the kinase activity of cyclin-D- and cyclin-E-associated Cdks and blocked p130 phosphorylation. TGF-β also enhanced the stability of p130, suggesting that hypophosphorylation of p130 and increased stability of p130 contribute to p130-mediated G arrest in gastric-cancer cells. Our results demonstrate that p21 and p130 are major downstream targets of TGF-β in gastric-cancer cells and that a p21-G1 cyclin/Cdks-p130/E2F pathway mediates growth inhibition by TGF-β in these cells.
ISSN
0020-7136
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/(SICI)1097-0215(19991112)83:4<512::AID-IJC13>3.0.CO;2-Z
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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