{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["43(3)"],"submitter":["Sakai H"],"pubmed_abstract":["Previous studies have shown that phosphorylation of the retinoid X receptor-α (RXRα) is associated with the development of hepatocellular carcinoma (HCC). However, these findings were revealed using HCC cell lines that express phosphorylated-RXRα (p-RXRα) proteins; therefore, it remains unclear whether p-RXRα affects hepatocarcinogenesis in vivo. Therefore, to investigate the biological function of p-RXRα in vivo, we developed a doxycycline-inducible ES cell line and transgenic mouse, both of which overexpress the phosphomimetic mutant form of RXRα, T82D/S260D, in a doxycycline-dependent manner. We found that the development of liver tumors, especially high-grade adenoma and HCC, was enhanced in diethylnitrosamine (DEN)-treated T82D/S260D-inducible mice. Moreover, the increased incidence of liver tumors in the transgenic mice was attributable to the promotion of cell cycle progression. Interestingly, the expression of β-catenin protein and its target gene cyclin D1 was elevated in the liver tumors of DEN-treated T82D/S260D-inducible mice, concurrent with increased cytoplasmic and nuclear β-catenin protein expression, indicating its stabilization and transcriptional activation. These results indicate that p-RXRα promotes DEN-induced hepatocarcinogenesis in mice through the activation of the β-catenin signaling pathway, suggesting that p-RXRα may serve as a possible therapeutic target for HCC."],"journal":["Carcinogenesis"],"pagination":["254-263"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9036992"],"repository":["biostudies-literature"],"pubmed_title":["The phosphorylated retinoid X receptor-α promotes diethylnitrosamine-induced hepatocarcinogenesis in mice through the activation of β-catenin signaling pathway."],"pmcid":["PMC9036992"],"pubmed_authors":["Hara A","Sakai H","Shimizu M","Imai K","Tomita H","Yamada Y","Shirakami Y","Kubota M"],"additional_accession":[]},"is_claimable":false,"name":"The phosphorylated retinoid X receptor-α promotes diethylnitrosamine-induced hepatocarcinogenesis in mice through the activation of β-catenin signaling pathway.","description":"Previous studies have shown that phosphorylation of the retinoid X receptor-α (RXRα) is associated with the development of hepatocellular carcinoma (HCC). However, these findings were revealed using HCC cell lines that express phosphorylated-RXRα (p-RXRα) proteins; therefore, it remains unclear whether p-RXRα affects hepatocarcinogenesis in vivo. Therefore, to investigate the biological function of p-RXRα in vivo, we developed a doxycycline-inducible ES cell line and transgenic mouse, both of which overexpress the phosphomimetic mutant form of RXRα, T82D/S260D, in a doxycycline-dependent manner. We found that the development of liver tumors, especially high-grade adenoma and HCC, was enhanced in diethylnitrosamine (DEN)-treated T82D/S260D-inducible mice. Moreover, the increased incidence of liver tumors in the transgenic mice was attributable to the promotion of cell cycle progression. Interestingly, the expression of β-catenin protein and its target gene cyclin D1 was elevated in the liver tumors of DEN-treated T82D/S260D-inducible mice, concurrent with increased cytoplasmic and nuclear β-catenin protein expression, indicating its stabilization and transcriptional activation. These results indicate that p-RXRα promotes DEN-induced hepatocarcinogenesis in mice through the activation of the β-catenin signaling pathway, suggesting that p-RXRα may serve as a possible therapeutic target for HCC.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2025-04-21T16:44:54.203Z","creation":"2025-04-21T16:44:54.203Z"},"accession":"S-EPMC9036992","cross_references":{"pubmed":["34668523"],"doi":["10.1093/carcin/bgab099"]}}