| Summary: | 碩士 === 國立陽明大學 === 微生物及免疫學研究所 === 92 === Primary hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the precise molecular mechanisms of HCC pathogenesis are not clear. The comparison of gene expression profiles between primary normal human hepatocytes and primary hepatocellular carcinoma may yield some potential factors that contribute to the pathogenesis of HCC. In this thesis, we found that UK114, a 14.5 kD protein primarily found in liver and kidney, is significantly down-regulated in tumor tissue of HCC as compared to the adjacent normal tissue. Furthermore, the expression level of UK114 is shown to be correlated with the differentiation grade of HCC tissue. Normally, the UK114 expression level in HCC tumor cell lines, such as HepG2, HuH7 and Hep3B, is relatively low. Stable clones of HepG2 and HuH7 that express UK114 seems to have reduced tumorigenicity in vivo and the expression of UK114 is associated with the colony forming activity in vitro. However, the expression of UK114 does not alter the proliferation rate of the cell line in both stable clone and transient transfection model nor it affects the cell cycle patterns of the cell lines. We also investigate mechanism involved in the regulation of UK114 in HCC cell lines. Although our data does not provide a clear mechanism, it does not support the hypothesis that down-regulation of UK114 is mediated by hypermethylation or histone deacethylation. In summary, a large portion of HCC specimens show down-regulation of UK114, and the expression level correlated with the grade of the HCC. Even though over-expression of UK114 has no effect on cell growth, it reduced the in vitro colony forming activity and the in vivo tumorigenecity of the cell lines. We conclude that UK114 might play an important role in hepatocellular carcinogenesis.
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