Because this is the fourth case reported in which hepatitis B virus-associated rearrangements have affected chromosome 17, it is conceivable that a loss of important cellular genes (such as the p53 antioncogene on chromosome 17) may be a crucial step in hepatitis B virus-related hepatocarcinogenesis.
To elucidate the role of p53 mutation in hepatocarcinogenesis in Taiwan, a hepatitis B viral infection hyperendemic area, exons 5 to 8 of the p53 gene in the tumor tissue of 61 hepatocellular carcinomas were amplified and sequenced.
The expression of transforming growth factor alpha (TGF-alpha) was examined in a human hepatoblastoma cell line, Hep G2, which does not contain hepatitis B virus (HBV) DNA, and in the cell line 2.2.15, which was formed by the transfection of Hep G2 cells with the complete HBV DNA, to study the possibility that HBV and TGF-alpha could function as co-factors in hepatocarcinogenesis.
TGF-beta 1 mRNA was expressed at much higher levels in HCC tissues from all the cases compared with normal human liver, suggesting an association of the activated TGF-beta 1 gene transcription with hepatocarcinogenesis.
Characterization of high-molecular-mass forms of basic fibroblast growth factor produced by hepatocellular carcinoma cells: possible involvement of basic fibroblast growth factor in hepatocarcinogenesis.
Characterization of a transforming N-ras gene in the human hepatoma cell line Hep G2: additional evidence for the importance of c-myc and ras cooperation in hepatocarcinogenesis.
In four of the seven hepatomas, expression of fetal forms of insulin-like growth factor II transcripts was observed and may represent dedifferentiation of insulin-like growth factor II expression during hepatocarcinogenesis.
In order to examine the effect of alteration in methylation of the c-myc gene on hepatocarcinogenesis, the extent of methylation of the c-myc gene was examined in 24 tissues of hepatocellular carcinoma (HCC), 24 adjacent non-tumor liver tissues from the same patients and 16 control liver tissues by the use of restriction endonucleases.The following results were obtained.
We investigated insulin-like growth factor II (IGF-II) mRNA in three groups of human liver samples including primary liver cancers, benign liver tumors and cirrhosis; indeed these pathological conditions would allow us to distinguish between different steps in liver carcinogenesis.
These mutations give rise to truncated receptor protein and significant amino acid substitutions, and provide evidence that the M6P/IGF2R gene functions as a tumour suppressor in human liver carcinogenesis.
The loss of responsiveness of hepatocytes to TGF-beta has been implicated in hepatocarcinogenesis and could result from a loss in the expression of either the TGF-beta receptors or the M6-P/IGF-IIr.
We suggest that the activation of insulin-like growth factor II gene and its overexpression may be a crucial step in the processes of hepatitis B virus-associated hepatocarcinogenesis and that the X gene product may activate the insulin-like growth factor II gene through a transactivation mechanism.