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 cha in leading to control of cell proliferation was studied in the H4IIE r at hepatoma cell line by inhibiting expression of the kinase with anti sense oligodeoxyribonucleotide directed against Raf-1 mRNA, Antisense oligonucleotide was found to reduce (at 2 mu M) or completely block (a t 15 mu M) the stimulation by insulin of DNA synthesis, measured as th ymidine incorporation. The residual DNA synthesis seen in the absence of insulin stimulation was also inhibited by the Raf-1 kinase antisens e oligonucleotide.