Early gene responses associated with transforming growth factor-beta 1 growth inhibition and autoinduction in MCF-7 breast adenocarcinoma cells

Abstract

In the human breast carcinoma cell line (MCF-7), exogenous TGF-beta 1 induces a dose-dependent inhibition of cell proliferation. In a MCF-7 cell subline [MCF-7(-)], which has an undetectable level of type II TGF-beta receptor, exogenous TGF-beta 1 does not inhibit cell proliferation but is still able to induce its own message. In both cell lines, TGF-beta 1 stimulates expression of c-jun, whereas a rapid, transient and marked increase in c-fos mRNA is only observed in the MCF-7 cells sensitive to the growth inhibitory effect of TGF-beta 1. Depletion of protein kinase C abolishes the c-fos but not the c-jun response to TGF-beta 1. Our results suggest that growth inhibition and autoinduction by TGF-beta 1 are mediated by different signalling pathways. In addition, a PKC-dependent increase in c-fos expression seems to be associated with the growth inhibitory effect of TGF-beta 1.