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Overexpression of orphan G‐protein–coupled receptor, Gpr49 , in human hepatocellular carcinomas with β‐catenin mutations
Author(s) -
Yamamoto Yoshiya,
Sakamoto Michiie,
Fujii Gen,
Tsuiji Hitomi,
Kenetaka Kengo,
Asaka Masahiro,
Hirohashi Setsuo
Publication year - 2003
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2003.50029
Subject(s) - hccs , wnt signaling pathway , carcinogenesis , cancer research , biology , hepatocellular carcinoma , exon , gene , microbiology and biotechnology , beta catenin , nuclear receptor , transcription factor , genetics
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.