Overexpression of orphan G-protein-coupled receptor, Gpr49, in human hepatocellular carcinomas with β-catenin mutations

Yoshiya Yamamoto, Michiie Sakamoto, Gen Fujii, Hitomi Tsuiji, Kengo Kanetaka, Masahiro Asaka, Setsuo Hirohashi

Research output: Contribution to journalArticlepeer-review

189 Citations (Scopus)


To identify the genes responsible for carcinogenesis and progression of hepatocellular carcinoma (HCC), we screened differentially expressed genes in several human HCC cell lines. Among these genes, Gpr49 was up-regulated in PLC/PRF/5 and HepG2. Gpr49 is a member of the glycoprotein hormone receptor subfamily, which includes the thyroid-stimulating hormone receptor (TSHR). However, Gpr49 remains to be an orphan G-protein-coupled receptor. By real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis, overexpression (>3-fold increase compared with the corresponding noncancerous liver tissue) of Gpr49 mRNA was observed in 18 of 38 (47%) HCCs compared with corresponding noncancerous livers. Clinicopathologically, overexpression of Gpr49 was frequently observed in HCC with mutation in β-catenin exon 3 (14 of 16 cases, 87.5%). Moreover, introduction of mutant β-catenin into mouse hepatocytes in culture caused up-regulation of the Gpr49 mouse homologue. Therefore, Gpr49 is likely to be a target gene activated by Wnt-signaling in HCC. In conclusion, although much is still unknown, Gpr49 may be critically involved in the development of HCCs with β-catenin mutations and has the potential to be a new therapeutic target in the treatment of HCC.

Original languageEnglish
Pages (from-to)528-533
Number of pages6
Issue number3
Publication statusPublished - 2003 Mar 1
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology


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