Transforming growth factor-β1 inhibits cyclin D1 expression in intestinal epithelial cells

T. C. Ko, H. M. Sheng, D. Reisman, E. A. Thompson, R. D. Beauchamp

Research output: Contribution to journalArticle

138 Scopus citations

Abstract

Transforming growth factor-β1 (TGP-β1) 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-β1 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-β1 treatment. In exponentially growing cultures, TGF-β1 blocked DNA synthesis and suppressed cyclin D1 mRNA and protein expression, whereas the levels of cyclins D2, D3 and Cdk4 remained relatively unchanged. TGF-β1 was also added to G0-synchronized IEC-6 cells after serum stimulation. TGF-β1 prevention of G1 progression was associated with an inhibition of cyclin D1 protein expression. Cyclin D3 levels were not affected by TGF-β1 during G1 traverse. Our results suggest that cyclin D/ Cdk4 is a crucial target of TGF-β1 and that regulation of this kinase is mediated through cyclin D1 in intestinal epithelial cells.

Original languageEnglish (US)
Pages (from-to)177-184
Number of pages8
JournalOncogene
Volume10
Issue number1
StatePublished - Jan 1 1995

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Keywords

  • Cell cycle
  • Cyclin
  • Cyclin-dependent kinase
  • Epithelial cell
  • Gene expression
  • TGF-β

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Ko, T. C., Sheng, H. M., Reisman, D., Thompson, E. A., & Beauchamp, R. D. (1995). Transforming growth factor-β1 inhibits cyclin D1 expression in intestinal epithelial cells. Oncogene, 10(1), 177-184.