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 p21WAF1/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 p21WAF1/CIP1 nuclear accumulation.
