Bedeutung von PACS-2 für die Karzinogenese von Hepatozyten

authored by
Kirstin Hanak
supervised by
Arndt Vogel

Liver cancer, particularly hepatocellular carcinoma (HCC), is the fifth most common tumerous disease and causes every second death related to neoplasia. While in Africa and Asia infections of hepatitis B and C cause hepatocellular carcinoma, in Europe and Northern America excessive consumption of food and alcohol lead to fatty liver, fibrosis and cirrhosis and over time to tumours in the liver. Until now diagnosis of liver cancer mostly occurs very late when therapy becomes delicate or impossible. To analyze the importance of PACS2 and its loss in hepatocarcinogenesis, a murine model was chosen to induce liver damage chemically via Diethylnitrosamine (DEN) that causes hepatocarcinogenesis in the process of time. Wildtype mice (PACS2+/+) and mice with genetic knockout of PACS2 (PACS2-/-) with and without (control) DEN-treatment were analyzed for liver damage, ability of regeneration, sensitivity to apoptosis, hepatitis and tumour development. It was shown that the used low dose of DEN in PACS2+/+- and PACS2-/--mice leads to a very mild liver damage and without detectable hepatitis to liver tumours. In PACS2-/--mice hepatocarcinogenesis was delayed, 12 months after DEN-treatment this difference was no longer present. After Jo2-induced apoptosis loss of PACS2 showed a gain of survival as DEN-treated knockout-mice survived a lot longer than animals of all other groups. An influence of PACS2 on regenerative capability was not observed. The delayed development of tumours is presumably attributed to a lesser extend of hepatocyte damage after DEN. The hyperplasia of PACS2-/--hepatocytes in the preneoplastic phase is reasoned in the mTOR-signaling pathway but indicates no connection to the delayed hepatocarcinogenesis. So PACS2 exhibits potential in understanding the multiple signaling pathways in the development of liver cancer but not in prevention or therapy of HCC.

Institute of Plant Genetics
Doctoral thesis
No. of pages
Publication date
Publication status
Sustainable Development Goals
SDG 3 - Good Health and Well-being
Electronic version(s) (Access: Open)