biostudies-literatureXie YNational Institute of Environmental Health SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNIDDK NIH HHSNIEHS NIH HHSNCI NIH HHS1123-1139https://www.ebi.ac.uk/biostudies/studies/S-EPMC9035576biostudies-literatureUnknown6(5)The oxysterol receptor liver X receptor (LXR) is a nuclear receptor best known for its function in the regulation of lipid and cholesterol metabolism. LXRs, both the α and β isoforms, have been suggested as potential therapeutic targets for several cancer types. However, there was a lack of report on whether and how LXRα plays a role in the development of hepatocellular carcinoma (HCC). In the current study, we found that systemic activation of LXRα in the VP-LXRα knock-in (LXRαKI) mice or hepatocyte-specific activation of LXRα in the VP-LXRα transgenic mice sensitized mice to liver tumorigenesis induced by the combined treatment of diethylnitrosamine (DEN) and 3,3',5,5'-tetrachloro-1,4-bis (pyridyloxy) benzene (TCPOBOP). Mechanistically, the LXRα-responsive up-regulation of interleukin-6 Hepatology communicationsChronic Activation of LXRα Sensitizes Mice to Hepatocellular Carcinoma.PMC9035576P30 DK120531DK117370P30 CA047904R35 ES030429ES030429R01 DK117370Xie WGuan JXu MXie YXu PBell AMa XZhang MMonga SPYang DWang JLu BLiu YZhu JSun RGao LLu PRen SCai XfalseChronic Activation of LXRα Sensitizes Mice to Hepatocellular Carcinoma.The oxysterol receptor liver X receptor (LXR) is a nuclear receptor best known for its function in the regulation of lipid and cholesterol metabolism. LXRs, both the α and β isoforms, have been suggested as potential therapeutic targets for several cancer types. However, there was a lack of report on whether and how LXRα plays a role in the development of hepatocellular carcinoma (HCC). In the current study, we found that systemic activation of LXRα in the VP-LXRα knock-in (LXRαKI) mice or hepatocyte-specific activation of LXRα in the VP-LXRα transgenic mice sensitized mice to liver tumorigenesis induced by the combined treatment of diethylnitrosamine (DEN) and 3,3',5,5'-tetrachloro-1,4-bis (pyridyloxy) benzene (TCPOBOP). Mechanistically, the LXRα-responsive up-regulation of interleukin-6 2022-01-01T00:00:00Z2022 May2026-05-07T03:19:52.127Z2025-04-04T19:32:17.356ZS-EPMC90355763498165810.1002/hep4.1880