Reduced T-cadherin expression and promoter methylation are associated with the development and progression of hepatocellular carcinoma

Qun Yan, Zhi Fa Zhang, Xiao Ping Chen, David H. Gutmann, Min Xiong, Zhen Yu Xiao, Zhi Yong Huang

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Loss of T-cadherin expression has been reported in a number of human cancers. We previously reported that T-cadherin re-expression suppressed cell growth and motility in glioma. Here, we report that the T-cadherin expression was significantly decreased in human hepatocellular carcinoma (HCC) compared to adjacent normal liver. In addition, T-cadherin expression in HCC with metastasis was significantly lower than in HCC without metastasis. To determine the mechanism underlying the reduced T-cadherin expression in HCC, we examined T-cadherin promoter methylation. We found that methylation of the T-cadherin promoter was present in 40% of HCC, but absent in all adjacent liver tissues. In the HCC with T-cadherin promoter methylation, the T-cadherin expression was significantly decreased compared to HCC without methylation. To provide a functional link between T-cadherin promoter methylation and T-cadherin growth regulation, we used the HepG2 hepatoma cell line that exhibits T-cadherin promoter methylation. Treatment of HepG2 cells with the demethylating agent 5-aza-2-deoxycytidine resulted in increased T-cadherin expression and reduced cell proliferation. These results demonstrate that the T-cadherin down-regulation by promoter methylation is associated with the development and progression of HCC, and suggest that T-cadherin is an important tumor suppressor in liver cancer.

Original languageEnglish
Pages (from-to)1057-1063
Number of pages7
JournalInternational journal of oncology
Volume32
Issue number5
DOIs
StatePublished - May 2008

Keywords

  • Expression
  • Hepatocellular carcinoma
  • Methylation
  • T-cadherin

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