Effects of TGF‐β1 (transforming growth factor‐β1) on the cell cycle regulation of human breast adenocarcinoma (MCF‐7) cells

FEBS Letters

Valette, Annie¹  Mazars, Philippe¹  Baldin, Véronique¹  Ducommun, Bernard¹  Barboule, Nadia¹  Vidal, Simone¹ 

[1] Laboratoire de Pharmacologie et de Toxicologie Fondamentales, 205 route de Narbonne, 31077 Toulouse cedex, France

关键词: TGF-β;    Cell cycle regulation;    Cyclin-dependent kinase (Cdk);    p21WAF1/CIP1;    Adenocarcinoma;   

DOI  :  10.1016/0014-5793(95)00247-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The antiproliferative effects of TGF-β1 were investigated in a human breast adenocarcinoma cell line (MCF-7). We report that TGF-β1 inhibits proliferation through cell cycle arrest in G₁. A MCF -7 cell subline (MCF-7(-)), in which the type II TGF-β receptor is not detected, was shown to be resistant to TGF-β1 growth inhibitory effect. Cdk2 kinase activity was inhibited in the MCF-7 sensitive cell subline in parallel with the inhibition of cell cycle progression. In both sensitive and resistant cell lines, TGF-β1 treatment did not affect cdk2, cdk4, cyclin E and cyclin D1 mRNA and protein levels. However, in the MCF-7 sensitive cell subline, a time-dependent increase in cells positive for p21^WAF1/CIP1 nuclear localization was observed after TGF-β1 treatment. These findings suggest that TGF-β1 inhibition of MCF-7 cell proliferation is achieved through a type II receptor-dependent down-regulation of Cdk2 kinase activity without modification of Cdk and cyclin expression, but correlated with an increase in p21^WAF1/CIP1 nuclear accumulation.

【 授权许可】

Unknown