Robert Beauchamp
Principal Investigator
Last active: 10/31/2018

Transforming growth factor-beta 1 inhibits cyclin D1 expression in intestinal epithelial cells.

Ko TC, Sheng HM, Reisman D, Thompson EA, Beauchamp RD
Oncogene. 1995 10 (1): 177-84

PMID: 7824270

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.

MeSH Terms (12)

Animals Cell Division Cyclin D1 Cyclins Epithelial Cells Epithelium Gene Expression Regulation Intestine, Small Oncogene Proteins Rats RNA, Messenger Transforming Growth Factor beta

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