Inhibition of anchorage-independent cell growth, adhesion, and cyclin D1 gene expression by a dominant negative mutant of a tyrosine phosphatase.

摘要: PTP-S4/TC48 protein tyrosine phosphatase is localized in the nuclear and cytoplasmic membranes. To investigate role of PTP-S4 cell growth, adhesion, transformation, normal a catalytically inactive mutant form this were expressed polyoma virus-transformed F111 fibroblast line, PyF. Expression PyF cells resulted strong inhibition anchorage-independent growth soft agar but had no significant effect on liquid culture. Tumor formation nude mice was also reduced by PTP-S4. significantly increased tumor mice. Overexpression PTP-S2/TC45 (a splice variant that nuclear) did not inhibit cells. Mutant PTP-S4-expressing inhibited adhesion spreading tissue culture plates compared to control levels cyclin D1 A mRNA, whereas D2 mRNA level affected significantly. antisense strongly growth. Inhibition overcome large extent coexpression D1. These results suggest inhibits interfering with function upstream gene expression.