Growth control and gene expression in a new hepatocellular carcinoma cell line, Hep40: inhibitory actions of vitamin K

J Cell Physiol. 1995 Dec;165(3):459-67. doi: 10.1002/jcp.1041650303.


The growth characteristics of a newly established cell line, Hep40, derived from a human hepatoma are described. An absolute requirement was found for serum to mediate cell growth. Neither EGF, TGF-alpha, nor HGF altered cell growth in the presence or absence of serum. A partial suppression of cell growth was achieved by several TGF-beta family proteins. Affinity crosslinking gels using 125I-labeled TGF-beta showed a significant decrease in the TGF-beta cell-surface type II receptor in Hep40 cells, compared to the TGF-beta-sensitive Hep3B cell line. However, growth could be completely suppressed by addition of vitamins K to the culture medium in both Hep40 and several other hepatoma cell lines. Growth suppression by vitamins K was accompanied by an increased level of transcripts for c-myc, c-jun, and prothrombin genes, in contrast to the actions of TGF-beta 1 protein, which caused a decrease in the level of c-myc transcripts. These data show that this new human hepatoma cell line has partial resistance to growth inhibition by TGF-beta with a unique TGF-beta receptor defect. However, growth was completely suppressed by vitamins K. The differing gene expression patterns in response to TGF-beta as compared to vitamin K suggest that these two growth inhibitors act through differing pathways.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Division / drug effects
  • Cell Division / physiology
  • Epidermal Growth Factor / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Prothrombin / genetics
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-myc / antagonists & inhibitors
  • Proto-Oncogene Proteins c-myc / genetics
  • RNA, Messenger / analysis
  • Rats
  • Transforming Growth Factor alpha / pharmacology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / pharmacology
  • Tumor Cells, Cultured
  • Vitamin K / pharmacology*


  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Transforming Growth Factor alpha
  • Transforming Growth Factor beta
  • Vitamin K
  • Epidermal Growth Factor
  • Prothrombin