The development of novel therapy for hepatocellular carcinoma using RXR-alpha genetically modified mice

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19320
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Gifu University
• Principal Investigator: Sakai Hiroyasu 岐阜大学, 医学部附属病院, 助教 (40738259)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 肝細胞癌 / レチノイド / RXRα / 核内受容体 / 肝化学発癌

Outline of Final Research Achievements

The role of phosphorylated-RXRa (p-RXRa) on the development of liver tumorigenesis was investigated by using RXRa genetically modified mice. The transgenic mice were more susceptible to the treatment of diethylnitrosamine (DEN), and developed more liver tumors compared to the control mice. In addition, liver tumors observed in the transgenic mice had more PCNA positive cells, indicating that those tumors had high proliferative capacity. Besides, increased mRNA and protein expressions of cyclin D1 were observed in transgenic liver tumors, and the protein expressions of either p-Rb or PCNA, both of which are the downstream targets of cyclin D1, were also increased in those liver tumors. Interestingly, the transgenic liver tumors had more b-catenin protein expression, which regulates the expression of cyclin D1. Thus, these results indicate that the p-RXRa is associated with the development of DEN-induced liver tumorigenesis by promoting b-catenin/cyclin D1 signaling pathway.

Free Research Field

消化器内科