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Type V collagen is an epithelial cell cycle inhibitor that is induced by and mimics the effects of transforming
T V Parekh1, X W Wang, D M Makri-Werzen
1Preclinical Oncology Discovery, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936, USA.
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.