Promyelocytic leukaemia protein links DNA damage response and repair to hepatitis B virus-related hepatocarcinogenesis.

摘要: DNA damage response and repair pathways are important barriers to carcinogenesis. Here, we show that promyelocytic leukaemia (PML, also known as TRIM19), involved in sensing executing homologous recombination repair, is down-regulated non-tumour liver cells surrounding hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). No PML mutation or deletion was found HBV-infected HCC cells. Immunohistochemical analysis of biopsies from patients with breast cancer HBV reactivation after chemotherapy revealed up-regulation exacerbation normal tissue (functional PML), down-regulation peritumour associated high HBsAg accumulation low replication activity (suppressive heterogeneous nuclear expression lost were non-reactive (dysregulated PML). Loss HBsAg-transgenic mice promoted chromosome breaks accelerated the body fat development a steatosis–dysplasia–adenoma–carcinoma sequence an inflammation-independent male-predominant manner, compared knock-out during same time period. These results indicate deficiency facilitates genomic instability promotes HBsAg-related hepatocarcinogenesis, which involves androgen lipid metabolism. findings uncover novel link between HBV-related tumourigenesis, Copyright © 2013 Pathological Society Great Britain Ireland. Published by John Wiley & Sons, Ltd.