Transforming Growth Factor-Beta 1 Inhibits Cyclin D1 Expression in Intestinal Epithelial Cells

Oncogene. 1995 Jan 5;10(1):177-84.

Abstract

Transforming growth factor-beta 1 (TGF-beta 1) inhibits most epithelial cell types by blocking cell cycle progression during the G1 phase. D cyclins are normally expressed during G1 and are regulators of G1 progression. One of the crucial functions of D cyclins is their ability to bind to a cyclin-dependent kinase (Cdk4). In mink lung epithelial cells, TGF-beta 1 inhibits Cdk4 expression. We have measured cell cycle progression and D cyclins and Cdk4 expression in non-transformed rat intestinal epithelial cell lines (IEC-6 and RIE-1) after TGF-beta 1 treatment. In exponentially growing cultures, TGF-beta 1 blocked DNA synthesis and suppressed cyclin D1 mRNA and protein expression, whereas the levels of cyclins D2, D3 and Cdk4 remained relatively unchanged. TGF-beta 1 was also added to G0-synchronized IEC-6 cells after serum stimulation. TGF-beta 1 prevention of G1 progression was associated with an inhibition of cyclin D1 protein expression. Cyclin D3 levels were not affected by TGF-beta 1 during G1 traverse. Our results suggest that cyclin D/Cdk4 is a crucial target of TGF-beta 1 and that regulation of this kinase is mediated through cyclin D1 in intestinal epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division
  • Cyclin D1
  • Cyclins / antagonists & inhibitors*
  • Cyclins / genetics
  • Epithelial Cells
  • Epithelium / metabolism
  • Gene Expression Regulation / drug effects
  • Intestine, Small / cytology
  • Intestine, Small / metabolism*
  • Oncogene Proteins / antagonists & inhibitors*
  • Oncogene Proteins / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Cyclins
  • Oncogene Proteins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Cyclin D1