Effects of TGF-beta 1 (transforming growth factor-beta 1) on the cell cycle regulation of human breast adenocarcinoma (MCF-7) cells

FEBS Lett. 1995 Apr 10;362(3):295-300. doi: 10.1016/0014-5793(95)00247-7.

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