Constitutive overexpression of c-fos protein in rat liver epithelial cells decreases TGF-β synthesis and increases TGF-β1 receptors

AbstractWe have previously shown that rat liver epithelial cells were more sensitive to TGF-β1 when they were transfected with c-fos cDNA. We analyzed the production of TGF-β and TGF-β1 binding proteins in transfected and parental cells. TGF-β-like activity released in the medium was reduced in c-fos expressing cells. TGF-β1 binding sites were more numerous in transfected cells (× 3).Cross-linking studies confirmed that c-fos transfected cells showed increased binding of 125I-TGF-β1 to membrane binding sites corresponding to type I, II and III receptors. Transfected cells internalized and degraded 125I-TGF-β1 more rapidly than parental cells. TGF-β1 incubation rapidly down-regulated the receptors. In parental cells, the down-regulation was total, while in transfected cells, a few binding proteins could still be detected. The c-fos cell line is an interesting tool in analysing the mechanism of action of TGF-β