TGF-?-induced cell-cycle arrest through the p21WAF1/CIP1-G1 cyclin/Cdks-p130 pathway in gastric-carcinoma cells
Open Access
- 10 November 1999
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 83 (4) , 512-517
- https://doi.org/10.1002/(sici)1097-0215(19991112)83:4<512::aid-ijc13>3.0.co;2-z
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 p21WAF1/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 G1 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. Int. J. Cancer 83:512–517, 1999.Keywords
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