GROWTH-CONTROL AND GENE-EXPRESSION IN A NEW HEPATOCELLULAR-CARCINOMA CELL-LINE, HEP40 - INHIBITORY ACTIONS OF VITAMIN-K

The growth characteristics of a newly established cell line, Hep40, de rived from a human hepatoma are described. An absolute requirement was found for serum to mediate cell growth. Neither EGF, TGF-alpha, nor H GF altered cell growth in the presence or absence of serum. A partial suppression of cell growth was achieved by several TGF-beta family pro teins. Affinity crosslinking gels using I-125-labeled TGF-beta showed a significant decrease in the TGF-beta cell-surface type II receptor i n Hep40 cells, compared to the TGF-beta-sensitive Hep3B cell line. How ever, growth could be completely suppressed by addition of vitamins K to the culture medium in both Hep40 and several other hepatoma cell li nes. Growth suppression by vitamins K was accompanied by an increased level of transcripts for c-myc, c-jun, and prothrombin genes, in contr ast to the actions of TGF-beta 1 protein, which caused a decrease in t he level of c-myc transcripts. These data show that this new human hep atoma cell line has partial resistance to growth inhibition by TGF-bet a with a unique TGF-beta receptor defect. However, growth was complete ly 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. (C) 1995 Wiley-Liss, Inc.