SEARCH

SEARCH BY CITATION

Keywords:

  • breast cancer;
  • CDK2;
  • P21;
  • phospho linker Smad2;
  • Smad2;
  • TGF-β

Abstract

Transforming growth factor-β (TGF-β) is a potent inhibitor of the growth of normal mammary epithelial cells, and has a pleiotropic, context-dependent, concentration-dependent action. We found attenuation of TGF-β signalling in mammary adenoma carcinoma cells. Phosphorylation at the linker site of Smad2 occurred in a cooperative way during the attenuation of TGF-β signalling, and was associated with upregulation of CDK2 and cyclin D1. CDK2 inhibitor restored the anti-proliferative effect of TGF-β by upregulating p21, with inhibition of linker phosphorylation of Smad2. CDK2-mediated linker phosphorylation of Smad2 may be a plausible mechanism for the attenuation of TGF-β signalling in breast cancer.