DNA methylation-dependent regulation of TrkA, TrkB, and TrkC genes in human hepatocellular carcinoma |
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| Authors: | Jin Wook Lee Jong-Joo Kim Min Soo Son Byung Ho Cho Yong Kyun Kim Hyoung-Pyo |
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| Institution: | aLaboratory of Molecular Disease and Cell Regulation, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, Republic of Korea;bDepartment of Environmental Medical Biology, Institute of Tropical Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Republic of Korea;cDivision of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, 108 Pyung-dong, Jongro-gu, Seoul 110-746, Republic of Korea;dDepartment of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, 108 Pyung-dong, Jongro-gu, Seoul 110-746, Republic of Korea |
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| 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. |
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| Keywords: | Trk Hepatocellular carcinoma DNA methylation Twist |
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