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TGF-β-induced cell-cycle arrest through the p21WAF1/CIP1-G1 cyclin/Cdks-p130 pathway in gastric-carcinoma cells

✍ Scribed by Young D. Yoo; Ju-Youn Choi; Su-Jae Lee; Jun S. Kim; Byung-Re Min; Young I. Lee; Yoon-Koo Kang


Publisher
John Wiley and Sons
Year
1999
Tongue
French
Weight
211 KB
Volume
83
Category
Article
ISSN
0020-7136

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✦ Synopsis


Transforming growth factor-␤1 (TGF-␤) inhibits cell-cycle progression of many types of cells by arresting them in G

1 /S phase through inhibition of the active cyclin-Cdk complexes that lead to inhibition of Rb phosphorylation. In gastriccancer cells, SNU16, TGF-␤ 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-␤ also enhanced the stability of p130, suggesting that hypophosphorylation of p130 and increased stability of p130 contribute to p130-mediated G 1 arrest in gastric-cancer cells. Our results demonstrate that p21 and p130 are major downstream targets of TGF-␤ in gastric-cancer cells and that a p21-G 1 cyclin/Cdks-p130/E2F pathway mediates growth inhibition by TGF-␤ in these cells.