Transforming growth factor beta 1 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 beta 1 (TGF-beta 1), express TGF-beta receptors type I, type II, and type III. We report that TGF-beta 1 protein selectively increased steady-state levels of the mRNA for the serine/threonine kinase receptor 1 (SKR1), a member of the TGF-beta superfamily receptor genes in these cells, whereas TGF-beta 1 had little effect on expression of the TGF-beta 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-beta 1 to the cells, and enhanced message levels peaked at 12 h as long as TGF-beta 1 was present in the culture medium. Hep 3B-TR cells which were resistant to TGF-beta 1 due to lack of both TGF-beta receptors type I and type II, expressed SKR1 mRNA, but it was not induced by TGF-beta 1 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-beta 1 selectively induces SKR1 message at a transcriptional level by a positive regulator.
Pittsburgh Transplant Institute, University of Pittsburgh School of Medicine, PA 15260.
M
M
Inagaki
Z
Z
Wang
B I
BI
Carr
D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017978:Receptors, Growth Factor / Q000032:analysis / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D003609:Dactinomycin; D003513:Cycloheximide; D017346:Protein Serine-Threonine Kinases