DNA methylation-dependent regulation of TrkA, TrkB, and TrkC genes in human hepatocellular carcinoma

被引：30

作者：

Jin, Wook ^{[2
]}

Lee, Jong-Joo ^{[3
]}

Kim, Min Soo ^{[2
]}

Son, Byung Ho ^{[4
]}

Cho, Yong Kyun ^{[1
]}

Kim, Hyoung-Pyo ^{[3
]}

机构：

[1] Sungkyunkwan Univ, Sch Med, Kangbuk Samsung Hosp, Div Gastroenterol,Dept Internal Med, Seoul 110746, South Korea

[2] Gachon Univ Med & Sci, Lab Mol Dis & Cell Regulat, Lee Gil Ya Canc & Diabet Inst, Inchon, South Korea

[3] Yonsei Univ, Coll Med, Dept Environm Med Biol, Inst Trop Med,Brain Korea Project Med Sci 21, Seoul 120752, South Korea

[4] Sungkyunkwan Univ, Sch Med, Kangbuk Samsung Hosp, Dept Surg, Seoul 110746, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2011年 / 406卷 / 01期

关键词：

Trk; Hepatocellular carcinoma; DNA methylation; Twist; RECEPTOR TYROSINE KINASES; TUMOR-SUPPRESSOR GENE; HUMAN CANCER-CELLS; HUMAN NEUROBLASTOMAS; EXPRESSION; METASTASIS; GROWTH; THERAPY; TWIST; HYPERMETHYLATION;

D O I：

10.1016/j.bbrc.2011.01.116

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. Irks promoted the proliferation of HepG2 and induced expression of the metastatic regulator, Twist. These results suggest that Irks may contribute to growth and metastasis of liver cancer. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：89 / 95

页数：7

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