Abstract
The antiproliferative effects of TGF-beta 1 were investigated in a human breast adenocarcinoma cell line (MCF-7). We report that TGF-beta 1 inhibits proliferation through cell cycle arrest in G1. A MCF-7 cell subline (MCF-7(-)), in which the type II TGF-beta receptor is not detected, was shown to be resistant to TGF-beta 1 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-beta 1 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-beta 1 treatment. These findings suggest that TGF-beta 1 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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenocarcinoma
-
Breast Neoplasms
-
CDC2-CDC28 Kinases*
-
Cell Division / drug effects
-
Cell Nucleus / chemistry
-
Cyclin D1
-
Cyclin-Dependent Kinase 2
-
Cyclin-Dependent Kinase 4
-
Cyclin-Dependent Kinase Inhibitor p21
-
Cyclin-Dependent Kinases / genetics
-
Cyclin-Dependent Kinases / metabolism*
-
Cyclins / analysis
-
Cyclins / genetics
-
Cyclins / metabolism
-
Down-Regulation
-
G1 Phase / drug effects*
-
Gene Expression Regulation, Neoplastic / drug effects
-
Humans
-
Oncogene Proteins / genetics
-
Oncogene Proteins / metabolism
-
Protein Serine-Threonine Kinases / genetics
-
Protein Serine-Threonine Kinases / metabolism*
-
Proto-Oncogene Proteins*
-
RNA, Messenger / analysis
-
Receptor, Transforming Growth Factor-beta Type II
-
Receptors, Transforming Growth Factor beta / analysis
-
Transforming Growth Factor beta / pharmacology*
-
Tumor Cells, Cultured
Substances
-
CDKN1A protein, human
-
Cyclin-Dependent Kinase Inhibitor p21
-
Cyclins
-
Oncogene Proteins
-
Proto-Oncogene Proteins
-
RNA, Messenger
-
Receptors, Transforming Growth Factor beta
-
Transforming Growth Factor beta
-
Cyclin D1
-
Protein Serine-Threonine Kinases
-
CDC2-CDC28 Kinases
-
CDK2 protein, human
-
CDK4 protein, human
-
Cyclin-Dependent Kinase 2
-
Cyclin-Dependent Kinase 4
-
Cyclin-Dependent Kinases
-
Receptor, Transforming Growth Factor-beta Type II