Laboratory of Molecular Disease and Cell Regulation, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, Republic of Korea.
Biochem Biophys Res Commun. 2011 Mar 4;406(1):89-95. doi: 10.1016/j.bbrc.2011.01.116. Epub 2011 Feb 3.
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.
原肌球蛋白相关激酶 (Trk) 家族的神经营养因子受体，TrkA、TrkB 和 TrkC，已被牵连到人类癌症的生长和存活中。在这里，我们报告称 Trks 在来自患者和人类肝癌细胞系的肝癌中经常过表达。为了解释这种现象的潜在分子机制，我们在源自肝脏的正常和癌细胞系中检查了 TrkA、TrkB 和 TrkC 基因的 CpG 岛的 DNA 甲基化模式。在正常肝细胞系中，观察到启动子超甲基化与 TrkA、TrkB 和 TrkC 基因表达降低之间存在良好的相关性，这一结果得到了以下数据的支持：用 5-氮杂胞苷抑制 DNA 甲基化可恢复这些基因的表达。此外，Trks 促进了 HepG2 的增殖，并诱导了转移调节因子 Twist 的表达。这些结果表明 Trks 可能有助于肝癌的生长和转移。
