| セッション情報 | The 2nd JSGE International Topic Conference2）Animal Models of Hepatocellular Carcinoma |
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| タイトル | IT2-1：Telomerase and Liver Stem Cell Related Mouse Models of Hepatocarcinogenesis |
| 演者 | Lechel André（Department of Internal Medicine 1, Ulm University Hospital, Germany） |
| 共同演者 | |
| 抄録 | Liver cancer is the 6th most common cancer in the world and the 3rd most common cause of cancer related death worldwide. The main risk factors for liver cancer development are chronic HBV/HCV infections, alcohol abuse, and exposure to AFB1. During early stages of human carcinogenesis most epithelial cancers have been observed to transit through a crisis stage which is characterized by loss of p53 checkpoint function, telomere shortening, and aneuploidy. The p53 checkpoint function represents one of the most relevant tumor suppressor mechanisms. Additionally, p53 influences cellular differentiation and stem cell function. From liver cancer it is known that p53 mutations are associated with poorly differentiated tumors. Moreover there is evidence that 20-30% of liver tumors show features of mixed differentiation and show similarities to stem and progenitor cells in gene expression profiles. These findings have fueled the discussion whether stem and progenitor cells could represent the cell type of origin of liver cancer formation. Transgenic mouse models of hepatocellular carcinoma can lead to the identification of molecular key players and a better understanding of hepatocarcinogenesis. Mouse studies provided direct evidence that telomerase is a critical component for the in vivo progression of p53 mutated HCC with short telomeres, through limiting the accumulation of telomere dysfunction, the evolution of elevated aneuploidy, and activation of p53-independent checkpoints which suppresses hepatocarcinogenesis. Futhermore, we showed first experimental evidence that the liver specific deletion of p53 as a single genetic lesion can lead to the formation of liver tumors with a bilineal differentiation, stem cell features, and a complex dysregulation of Rb checkpoint genes. |
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