Effects of insulin on TGF-beta 1-induced cell growth inhibition in the human hepatoma cell lines.
The effects of insulin on cell growth control by transforming growth factor beta 1 (TGF-beta 1) in human hepatoma cell lines were studied. TGF-beta 1 inhibited cell growth and DNA synthesis of Hep3B cells but not that of HA22T/VGH cells. The cell cycle-dependent p34cdc2 kinase activity was inhibited by TGF-beta 1 in a dose-dependent manner in Hep3B cells. In contrast, the p34cdc2 kinase activity of HA22T/VGH cells was not regulated by TGF-beta 1. When insulin (10(-7) M) was added simultaneously with TGF-beta 1, we found that the inhibitory effects of TGF-beta 1 on cell growth and DNA synthesis in Hep3B cells was completely blocked and the p34cdc2 kinase activity of Hep3B cells was recovered after insulin administration. Thus, cell growth inhibition by TGF-beta 1 in Hep3B hepatoma cells can be antagonized by insulin and their interaction may play an important role in the tumor progression stage of hepatocarcinogenesis.
Hung
W C
WC
Department of Biochemistry, Kaohsiung Medical College, Taiwan, R.O.C.
Chuang
L Y
LY
Tsai
J H
JH
Chang
C C
CC
D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000473:pathology*; D010766:Phosphorylation; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007328:Insulin; D016212:Transforming Growth Factor beta; D016203:CDC2 Protein Kinase