Transforming growth factor β1 selectively increases gene expression of the serine/threonine kinase receptor 1 (SKR1) in human hepatoma cell lines

Human hepatoma cell lines (Hep 3B-TS, PLC/PRF/5, and Hep G2), sensitive to growth inhibition by transforming growth factor β1 (TGF-β1), express TGF-β receptors type I, type II, and type III. We report that TGF-β1 protein selectively increased steady-state levels of the mRNA for the serine/threonine kinase receptor 1 (SKR1), a member of the TGF-β superfamily receptor genes in these cells, whereas TGF-β1 had little effect on expression of the TGF-β receptor type II gene. This increase of SKR1 mRNA in Hep 3B-TS cells could be detected by Northern blot analysis within 3 h of addition of TGF-β1 to the cells, and enhanced message levels peaked at 12 h as long as TGF-β1 was present in the culture medium. Hep 3B-TR cells which were resistant to TGF-β1 due to lack of both TGF-β receptors type I and type II, expressed SKR1 mRNA, but it was not induced by TGF-β1 protein. The increased expression of SKR1 mRNA in the cells was actinomycin D-sensitive and was not dependent on new protein synthesis. The results indicate that TGF-β1 selectively induces SKR1 message at a transcriptional level by a positive regulator.