Characterization of a human hepatoma cell line with acquired resistance to growth inhibition by transforming growth factor beta 1 (TGF-beta 1).
A new cell line (Hep 3B-TR), which is resistant to growth-inhibition by transforming growth factor beta 1 (TGF-beta 1) up to 10 ng/ml (400 pM), was isolated from parental Hep 3B human hepatoma cells, which are sensitive to growth-inhibition by TGF-beta 1. In the presence of TGF-beta 1 (1 to 10 ng/ml), the growth of the parental cell line (Hep 3B-TS) was inhibited by more than 95%. Under the same conditions, the growth rate of the resistant clone (Hep 3B-TR) however, was identical in the presence or absence of TGF-beta 1 and was almost the same as that of the Hep 3B-TS cells in the absence of TGF-beta 1. Affinity crosslinking with 5 pM 125I-labeled TGF-beta 1 showed that the TGF-beta 1 receptors type I (TGF-beta RI) and type II (TGF-beta RII) were not present on the cell surface of the Hep 3B-TR cells, whereas they were present on the sensitive HEP 3B-TS cells. Hep 3B-TS cells had detectable TGF-beta RII mRNA, which was not found in Hep 3B-TR cells. RNA analysis showed different effects on the expression of TGF-beta 1, c-fos, c-myc, and protein disulfide isomerase (PDI) genes in the two cell lines in response to TGF-beta 1 protein. Addition of TGF-beta 1 (1 ng/ml) strongly increased the expression of TGF-beta 1 mRNA in Hep 3B-TS cells, but not in Hep 3B-TR cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Hasegawa
K
K
Pittsburgh Transplantation Institute, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA.
Wang
Z
Z
Inagaki
M
M
Carr
B I
BI
D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division; D003432:Cross-Linking Reagents; D004351:Drug Resistance; D015870:Gene Expression; D016762:Genes, fos; D016259:Genes, myc; D006801:Humans; D007535:Isomerases / Q000235:genetics; D008113:Liver Neoplasms / Q000473:pathology*; D019704:Protein Disulfide-Isomerases; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D003432:Cross-Linking Reagents; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007535:Isomerases; D019704:Protein Disulfide-Isomerases