Inhibition of Raf-1 kinase expression abolishes insulin stimulation of DNA synthesis in H4IIE hepatoma cells.
The involvement of Raf-1 kinase in the insulin signal transduction chain leading to control of cell proliferation was studied in the H4IIE rat hepatoma cell line by inhibiting expression of the kinase with antisense oligodeoxyribonucleotide directed against Raf-1 mRNA. Antisense oligonucleotide was found to reduce (at 2 microM) or completely block (at 15 microM) the stimulation by insulin of DNA synthesis, measured as thymidine incorporation. The residual DNA synthesis seen in the absence of insulin stimulation was also inhibited by the Raf-1 kinase antisense oligonucleotide.
Törnkvist
A
A
Department of Cell Biology, Faculty of Health Sciences, University of Linköping, Sweden.
Parpal
S
S
Gustavsson
J
J
Strålfors
P
P
D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D007328:Insulin / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D013552:Swine; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007328:Insulin; D008934:Mitogens; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf