PMID- 7824270 OWN - NLM STAT- MEDLINE DCOM- 19950214 LR - 20071114 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 10 IP - 1 DP - 1995 Jan 5 TI - Transforming growth factor-beta 1 inhibits cyclin D1 expression in intestinal epithelial cells. PG - 177-84 AB - 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. FAU - Ko, T C AU - Ko TC AD - Department of Surgery, University of Texas Medical Branch, Galveston 77555. FAU - Sheng, H M AU - Sheng HM FAU - Reisman, D AU - Reisman D FAU - Thompson, E A AU - Thompson EA FAU - Beauchamp, R D AU - Beauchamp RD LA - eng GR - CA 24347/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (Cyclins) RN - 0 (Oncogene Proteins) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta) RN - 136601-57-5 (Cyclin D1) SB - IM MH - Animals MH - Cell Division MH - Cyclin D1 MH - Cyclins/*antagonists & inhibitors/genetics MH - Epithelial Cells MH - Epithelium/metabolism MH - Gene Expression Regulation/drug effects MH - Intestine, Small/cytology/*metabolism MH - Oncogene Proteins/*antagonists & inhibitors/genetics MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Transforming Growth Factor beta/*pharmacology EDAT- 1995/01/05 00:00 MHDA- 1995/01/05 00:01 CRDT- 1995/01/05 00:00 PHST- 1995/01/05 00:00 [pubmed] PHST- 1995/01/05 00:01 [medline] PHST- 1995/01/05 00:00 [entrez] PST - ppublish SO - Oncogene. 1995 Jan 5;10(1):177-84.