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Promoter hypomethylation and reactivation of MAGE-A1 and MAGE-A3 genes in colorectal cancer cell lines and cancer tissues

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Publication Date
Keywords
  • Antigens
  • Neoplasm/*Genetics/Metabolism
  • Antimetabolites
  • Antineoplastic/Pharmacology
  • Azacitidine/Analogs & Derivatives/Pharmacology
  • Cell Line
  • Tumor
  • Colorectal Neoplasms/*Genetics/Metabolism/Pathology
  • *Dna Methylation
  • Dna
  • Neoplasm/Genetics/Metabolism
  • Gene Expression Regulation
  • Neoplastic/Genetics
  • Humans
  • Neoplasm Proteins/*Genetics/Metabolism
  • Promoter Regions
  • Genetic/*Genetics
  • Rna
  • Messenger/Genetics/Metabolism
  • Stomach Neoplasms/Genetics/Metabolism/Pathology

Abstract

AIM: To verify the expression and methylation status of the MAGE-A1 and MAGE-A3 genes in colorectal cancer tissues and cancer cell lines. METHODS: We evaluated promoter demethylation status of the MAGE-A1 and MAGE-A3 genes by RT-PCR analysis and methylation-specific PCR (MS-PCR), as well as sequencing analysis, after sodium bisulfite modification in 32 colorectal cancer cell lines and 87 cancer tissues. RESULTS: Of the 32 cell lines, MAGE-A1 and MAGE-A3 expressions were observed in 59% and 66%, respectively. Subsequent to sodium bisulfite modification and MS-PCR analysis, the promoter hypomethylation of MAGE-A1 and MAGE-A3 was confirmed in both at 81% each. Promoter hypomethylation of MAGE-A1 and MAGE-A3 in colorectal cancer tissues was observed in 43% and 77%, respectively. Hypomethylation of MAGE-A1 and MAGE-A3 genes in corresponding normal tissues were observed in 2% and 6%, respectively. CONCLUSION: The promoter hypomethylation of MAGE genes up-regulates its expression in colorectal carcinomas as well as in gastric cancers and might play a significant role in the development and progression of human colorectal carcinomas.

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