並列タイトル等TGFα,c-MYC，変異型CTNNB1遺伝子およびこれらの組み合わせはヌードマウスにおけるHep3B腫瘍形成に明確に作用する
タイトル（掲載誌）Medical Journal of Osaka University
一般注記doctoral
医学系研究科
Hepatocellular carcinoma (HCC) is the most common hepatic tumor worldwide and is a major cause of death in many countries. Although chronic viral infections and hepatotoxic agents are the major risk factors, the molecular pathogenesis of HCC remains largely unknown. Among model mice, TGFα/c-Myc transgenic mice develop human HCC-like tumors. Whole genome sequencing of HCC tumors from patients has shown that mutations to CTNNB1 (β-catenin) are the most frequent (15.9%). So in this study, we characterized the effects of TGFα, c-MYC and mutant CTNNB1 genes on the transplantable Hep3B cells. TGFα increased the tumor number after transplanting Hep3B cells. Mutant CTNNB1 changed the characteristics of Hep3B tumor cells into a disarranged structure with loose cell-cell contacts. And co-transduction of TGFα and mutant CTNNB1 synergistically increased the growth rate, size and weight of Hep3B tumors. Unexpectedly, c-MYC overexpression in the Hep3B cells induced apoptosis. Interestingly, TGFα+mutant CTNNB1+MYC-transduced cells grew very slowly and the tumor showed transdifferentiation into a cholangial duct. These results suggest that the interaction of these three genes determines the characteristics of Hep3B tumor. Overexpression of c-MYC by a lentivirus in c-MYC-upregulated HCC tumors might be used as a molecular targeted therapy.
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