title: DNA methylation-dependent regulation of TrkA, TrkB, and TrkC genes in human hepatocellular carcinoma.
abstract: The tropomyosin-related kinase (Trk) family of neurotrophin receptors, TrkA, TrkB and TrkC, has been implicated in the growth and survival of human cancers. Here we report that Trks are frequently overexpressed in hepatocellular carcinoma (HCC) from patients and human liver cancer cell lines. To unravel the underlying molecular mechanism(s) for this phenomenon, DNA methylation patterns of CpG islands in TrkA, TrkB, and TrkC genes were examined in normal and cancer cell lines derived from liver. A good correlation was observed between promoter hypermethylation and lower expression of TrkA, TrkB, and TrkC genes, which was supported by the data that inhibiting DNA methylation with 5-azacytidine restored expression of those genes in normal liver cell lines. Furthermore, Trks promoted the proliferation of HepG2 and induced expression of the metastatic regulator, Twist. These results suggest that Trks may contribute to growth and metastasis of liver cancer.
authors.affiliation: Laboratory of Molecular Disease and Cell Regulation, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, Republic of Korea.
authors.forename: Wook
authors.initials: W
authors.lastname: Jin
authors.forename: Jong-Joo
authors.initials: JJ
authors.lastname: Lee
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Kim
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Son
authors.forename: Yong Kyun
authors.initials: YK
authors.lastname: Cho
authors.forename: Hyoung-Pyo
authors.initials: HP
authors.lastname: Kim
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000494:pharmacology; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D019175:DNA Methylation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D020917:Receptor, trkA / Q000235:genetics*; D020813:Receptor, trkB / Q000235:genetics*; D020812:Receptor, trkC / Q000235:genetics*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D051879:Twist-Related Protein 1 / Q000235:genetics
chemical_list: D000964:Antimetabolites, Antineoplastic; D009687:Nuclear Proteins; D017475:Receptors, Nerve Growth Factor; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC; D001374:Azacitidine