Abstract 185: Protein expression of DNMT1, DNMT3a, and DNMT3b in human hepatocellular carcinoma

Abstract

Background/Aims: DNA methylation plays an important roles in the regulation of gene expression. Gene silencing by aberrant hypermethylation of CpG islands in gene promoter regions in frequently found in human cancers. By the assistance of DNA methyltransferases (DNMTs), methyl groups are transferred to promoter CpG islands, many tumor suppressor gene can be silenced by promoter CpG islands methylation. However, studies on DNMTs in hepatocellular carcinoma (HCC) are rare, and there are no immunohistochemical studies on the correlations with these expressions and HCC patient's suvival. Methods : We immunohistochemically examined the expression of DNMT1, DNMT3a and DNMT3b and the relationships between these expressions and histological grade, clinicopathological parameters and patient's survival in 95 patients with HCC. Results : DNMT1, DNMT3a and DNMT3b immunoreactivities were presented in nuclei of HCC cells. In the tumorous lesion, the number of positive immunoreactivities was 95/95 (100%) for DNMT1, 87/95 (92%) for DNMT3a and 81/95 (85%) for DNMT3b. The degree of each protein expression significantly correlated with tumor differentiation and intrahepatic metastasis, and only DNMT3a protein expression significantly correlated with portal vein imvolvement of tumor. Though there were no relations between the DNMTs expression and tumor size, over-expressions of DNMT3a and 3b proteins were associated with poor prognosis of HCC's patients. Moreover, the overall survival rate of patients group that showed over-expression of three DNMTs in tumorous lesion was significantly lower than it of other patients groups. Conclusion : DNMTs are involved in HCC progression, and their overexpression is associated with poor prognosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 185.

Antitumor activity of sevoflurane in HCC cell line is mediated by miR‐29a‐induced suppression of Dnmt3a

“…DNA methyltransferase 3 alpha (Dnmt3a) mutation establishes a predisposition to hematological malignancies by a DNA methylation‐dependent manner . However, Dnmt3a overexpression is observed in patients with HCC, which correlates with HCC progression and poor prognosis . Aberrant DNA methylation is considered a contributory factor to alter gene expression of tumor suppressors .…”

“…10 However, Dnmt3a overexpression is observed in patients with HCC, which correlates with HCC progression and poor prognosis. 11 Aberrant DNA methylation is considered a contributory factor to alter gene expression of tumor suppressors. 12 For instance, demethylation of phosphatase and tensin homolog (PTEN) promoter was detected in Dnmt3a-depleted HCC cells.…”