title: Type V collagen is an epithelial cell cycle inhibitor that is induced by and mimics the effects of transforming growth factor beta1.
abstract: The regulation of epithelial cell cycle progression by extracellular matrix proteins was investigated in mink lung epithelial cells (Mv1Lu cells) and primary human keratinocytes. Exogenous type V collagen was able to mimic all of the inhibitory effects of type 1 transforming growth factor beta (TGF-beta1). No significant inhibitory effect was observed with collagen types I, III, and IV; laminin; or fibronectin. The type V collagen used was not contaminated with TGF-betas. TGF-beta1 increased the rate of type V collagen protein secretion in Mv1Lu cells, which occurred coincident with DNA synthesis inhibition. Both TGF-beta1 and type V collagen inhibited retinoblastoma protein phosphorylation and the expression of cyclin-dependent kinase (cdk) 4 and cdk2, but not p27Kip expression. Mv1Lu cells constitutively expressing the SV40 T antigen or cdk4 were resistant to the inhibitory effects of both TGF-beta1 and type V collagen. Our results demonstrate that type V collagen is a novel and specific epithelial cell cycle inhibitor and suggest that it may act as an autocrine mediator of the inhibitory effects of TGF-beta1.
authors.affiliation: Preclinical Oncology Discovery, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936, USA.
authors.forename: T V
authors.initials: TV
authors.lastname: Parekh
authors.forename: X W
authors.initials: XW
authors.lastname: Wang
authors.forename: D M
authors.initials: DM
authors.lastname: Makri-Werzen
authors.forename: D S
authors.initials: DS
authors.lastname: Greenspan
authors.forename: M J
authors.initials: MJ
authors.lastname: Newman
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology*; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D005786:Gene Expression Regulation; D006801:Humans; D008907:Mink; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D016212:Transforming Growth Factor beta; D003094:Collagen; D004247:DNA; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases