O 6 -Methylguanine-DNA methyltransferase (MGMT) is a major determinant of susceptibility to methylating carcinogens and of tumor resistance to anticancer methylating and chloroethylating drugs. The silencing of MGMT expression that occurs in 20-30% of human tumor lines is tightly linked to methylati
The E-cadherin gene is silenced by CpG methylation in human hepatocellular carcinomas
โ Scribed by Yae Kanai; Saori Ushijima; Ai-Min Hui; Atsushi Ochiai; Hitoshi Tsuda; Michiie Sakamoto; Setsuo Hirohashi
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- French
- Weight
- 214 KB
- Volume
- 71
- Category
- Article
- ISSN
- 0020-7136
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โฆ Synopsis
Our study was designed to clarify the significance of silencing the E-cadherin gene, which is located on 16q22.1, due to CpG methylation during hepatocarcinogenesis. The CpG methylation status of primary hepatocellular carcinomas (HCCs) and corresponding liver tissues showing chronic hepatitis or cirrhosis, which are widely considered to be precancerous conditions, were assessed by digesting DNA with methylation-sensitive and non-sensitive restriction enzymes. CpG methylation around the promoter region of the E-cadherin gene was detected in 46% of liver tissues showing chronic hepatitis or cirrhosis and 67% of HCCs examined. Immunohistochemical examination revealed reduced E-cadherin expression in 59% of HCCs examined. CpG methylation around the promoter region correlated significantly with reduced E-cadherin expression in HCCs (p < 0.05). CpG methylation around the promoter region, which increases during the progression from a precancerous condition to HCC, may participate in hepatocarcinogenesis through reduction of E-cadherin expression, resulting in loss of intercellular adhesiveness and destruction of tissue morphology.
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