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Effects of TGF‐β1 (transforming growth factor‐β1) on the cell cycle regulation of human breast adenocarcinoma (MCF‐7) cells
Author(s) -
Mazars Philippe,
Barboule Nadia,
Baldin Véronique,
Vidal Simone,
Ducommun Bernard,
Valette Annie
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00247-7
Subject(s) - mcf 7 , cyclin dependent kinase 2 , cyclin dependent kinase , cell cycle , cyclin e , cell growth , transforming growth factor , transforming growth factor beta , biology , cyclin d1 , cancer research , cyclin , microbiology and biotechnology , cyclin d , cell culture , kinase , cyclin a , chemistry , endocrinology , cell , protein kinase a , cancer cell , biochemistry , cancer , human breast , genetics
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 G 1 . 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.