Suppression of decorin expression and partial induction of anchorage-independent growth by the v-src oncogene in human fibroblasts.

To determine its role in cell transformations, the v-src oncogene was introduced into the human foetal diploid fibroblasts MRC-5 and into MRC-SV1, a simian virus 40 (SV40)-transformed cell line derived from them. Infected cells were found to contain stably integrated intact proviruses, as determined by Southern blot analysis. Although highly expressed, v-src did not change the morphology or growth patterns of MRC-5 cells and failed to induce foci or alter their saturation densities. However, overexpression of v-src reduced the plating efficiencies of MRC-5 and induced anchorage-independent growth in a low but significant number of cells. Northern blot analysis showed that v-src selectively abolished the expression of decorin, a small dermatan/chondroitin sulphate proteoglycan that interacts with extracellular-matrix components and modulates collagen-fibril formation and the activity of transforming growth factor (TGF) beta1. Addition of herbimycin A, a potent pp60src tyrosine-kinase inhibitor, resulted in the reexpression of decorin in MRC-5 carrying v-src. There were no changes in the expressions of fibronectin, procollagen type I, or tissue plasminogen activator, an activator of extracellular-matrix-degrading enzymes. Moreover, v-src did not alter the expressions of the epidermal-growth-factor receptor or TGFbeta1 or reduce the growth-factor requirements of MRC-5 fibroblasts. MRC-5 and MRC-SV1 expressing v-src remained non-tumourigenic when injected into nude mice. Constitutive expression of v-src did not alter the mRNA levels of c-jun and junB, suggesting that the effects of the oncogene are not mediated by AP-1. Decorin gene expression has been shown previously to be maximal in quiescent cells and virtually absent in transformed ones. Our data indicate that the ability to synthesise decorin can be suppressed in human fibroblasts without their becoming transformed, and that the relations between decorin synthesis and growth controls need further clarification.