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 sensitive to TGF-beta 1 when they were transfected with c-fos cDNA. We analyzed the production of TGF-beta and TGF-beta 1 binding proteins in transfected and parental cells. TGF-beta-like activity released in the medium was reduced in c-fos expressing cells. TGF-beta 1 binding sites were more numerous in transfected cells (x3). Cross-linking studies confirmed that c-fos transfected cells showed increased binding of 125I-TGF-beta 1 to membrane binding sites corresponding to type I, II and III receptors. Transfected cells internalized and degraded 125I-TGF-beta 1 more rapidly than parental cells. TGF-beta 1 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-beta.
Mercier
T
T
Laboratoire de Nutrition et Sécurité Alimentaire, INRA-CRJ, Jouy-en-Josas, France.
Gaillard-Sanchez
I
I
Martel
P
P
Seillan-Heberden
C
C
D030201:Activin Receptors, Type I; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018076:DNA, Complementary; D004848:Epithelium / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D018076:DNA, Complementary; D016760:Proto-Oncogene Proteins c-fos; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat