Hila Barash1, Eitan Gross2, Natalie Corchia1, Irit Cohen1, Daniel Goldenberg1, Eithan Galun1, Rinat Abramovitch1,3
1Goldyne Savad Institute for Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel; 2Pediatric Surgery, Hadassah Hebrew University Medical Center, Jerusalem, Israel; 3MRI/MRS lab HBRC, Hadassah Hebrew University Medical Center, Jerusalem, Israel
Hepatocellular-carcinoma (HCC) is the third leading cause of cancer mortality and considered to be the outcome of chronic liver inflammation. Surgical-resection is the preferred treatment for HCC; however, survival rates are suboptimal due to tumor recurrence. Our objective was to understand the molecular mechanisms linking liver regeneration under chronic-inflammation to tumorigenesis. Mdr2-knockout mice, had undergone partial-hepatectomy, and experienced enhanced hepatocarcinogenesis. Yet, liver regeneration was severely attenuated. The inflamed livers had elevated levels of double-stranded DNA breaks resulting in hepatocyte apoptosis and cell-cycle arrest. We propose that under the proliferative stress, the genomic-unstable-hepatocytes reenter the cell cycle, causing the enhanced tumorigenesis.