Accelerated carcinogenesis following liver regeneration is associated with chronic inflammation-induced double-strand DNA breaks.

ABSTRACT: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide and is considered to be the outcome of chronic liver inflammation. Currently, the main treatment for HCC is surgical resection. However, survival rates are suboptimal partially because of tumor recurrence in the remaining liver. Our aim was to understand the molecular mechanisms linking liver regeneration under chronic inflammation to hepatic tumorigenesis. Mdr2-KO mice, a model of inflammation-associated cancer, underwent partial hepatectomy (PHx), which led to enhanced hepatocarcinogenesis. Moreover, liver regeneration in these mice was severely attenuated. We demonstrate the activation of the DNA damage-response machinery and increased genomic instability during early liver inflammatory stages result

SUBMITTER: Barash H 

PROVIDER: S-EPMC2836653 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature