CONSTITUTIVE OVEREXPRESSION OF C-FOS PROTEIN IN RAT-LIVER EPITHELIAL-CELLS DECREASES TGF-BETA SYNTHESIS AND INCREASES TGF-BETA(1) RECEPTORS

We have previously shown that rat liver epithelial cells were more sen sitive to TGF-beta(1) when they were transfected with c-fos cDNA. We a nalyzed the production of TGF-beta and TGF-beta(1) binding proteins in transfected and parental cells. TGF-beta-like activity released in th e medium was reduced in c-fos expressing cells. TGF-beta(1) binding si tes were more numerous in transfected cells (X3). Cross-linking studie s confirmed that c-fos transfected cells showed increased binding of I -125-TGF-beta 1 to membrane binding sites corresponding to type I, II and III receptors. Transfected cells internalized and degraded I-125-T GF-beta(1) more rapidly than parental cells. TGF-beta(1) incubation ra pidly down-regulated the receptors. In parental cells, the down-regula tion was total, while in transfected cells, a few binding proteins cou ld still be detected. The c-fos cell line is an interesting tool in an alysing mechanism of action of TGF-beta.