TRANSFORMING GROWTH-FACTOR-BETA-1 INHIBITS HUMAN KERATINOCYTE PROLIFERATION BY UP-REGULATION OF A RECEPTOR-TYPE TYROSINE PHOSPHATASE R-PTP-KAPPA GENE-EXPRESSION

We studied regulation of a receptor-type tyrosine phosphatase R-PTP-ka ppa gene expression in a human keratinocyte cell line, HaCaT. Addition of TGF-beta 1 to the HaCaT cells markedly induced the expression of R -PTP-kappa mRNA in a time- and dose-dependent manner. The induction of R-PTP-kappa mRNA expression was observed at a dose as low as 0.02 ng/ ml TGF-beta 1 and reached a peak at 2 ng/ml TGF-beta 1 after 6 h treat ment. The TGF-beta 1-induced R-PTP-kappa mRNA expression was suppresse d by sodium orthovanadate, a tyrosine phosphatase inhibitor, and H7, a serine/threonine kinase inhibitor, but not by genistein, a tyrosine k inase inhibitor. In addition, the inducing effect is not dependent on de novo protein synthesis. Taken together, these results suggest that TGF-beta 1 inhibits the human keratinocyte proliferation in vitro, pos sibly through induction of R-PTP-kappa gene expression. (C) 1996 Acade mic Press, Inc.