Transforming growth factor-beta 1 inhibits cyclin D1 expression in intestinal epithelial cells.
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.
Ko
T C
TC
Department of Surgery, University of Texas Medical Branch, Galveston 77555.
Sheng
H M
HM
Reisman
D
D
Thompson
E A
EA
Beauchamp
R D
RD
D000818:Animals; D002455:Cell Division; D019938:Cyclin D1; D016213:Cyclins / Q000037:antagonists & inhibitors* / Q000235:genetics; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism*; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016213:Cyclins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019938:Cyclin D1