TY - JOUR
T1 - Overexpression of orphan G-protein-coupled receptor, Gpr49, in human hepatocellular carcinomas with β-catenin mutations
AU - Yamamoto, Yoshiya
AU - Sakamoto, Michiie
AU - Fujii, Gen
AU - Tsuiji, Hitomi
AU - Kanetaka, Kengo
AU - Asaka, Masahiro
AU - Hirohashi, Setsuo
N1 - Funding Information:
Supported in part by a Grant-in-Aid for Research on Human Genome and Gene therapy and a Grant-in-Aid for the Second Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan. Y.Y. and K.K. are the recipients of Research Resident Fellowships from the Foundation for Promotion of Cancer Research in Japan. H.T. is a domestic research fellow supported by Japan Science and Technology Corporation.
PY - 2003/3/1
Y1 - 2003/3/1
N2 - 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.
AB - 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.
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U2 - 10.1053/jhep.2003.50029
DO - 10.1053/jhep.2003.50029
M3 - Article
C2 - 12601349
AN - SCOPUS:0037369658
SN - 0270-9139
VL - 37
SP - 528
EP - 533
JO - Hepatology
JF - Hepatology
IS - 3
ER -