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

World J Gastroenterol. 2006 Sep 21;12(35):5651-7. doi: 10.3748/wjg.v12.i35.5651.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Antimetabolites, Antineoplastic / pharmacology
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • DNA Methylation*
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism
  • Decitabine
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Melanoma-Specific Antigens
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology

Substances

  • Antigens, Neoplasm
  • Antimetabolites, Antineoplastic
  • DNA, Neoplasm
  • MAGEA1 protein, human
  • MAGEA3 protein, human
  • Melanoma-Specific Antigens
  • Neoplasm Proteins
  • RNA, Messenger
  • Decitabine
  • Azacitidine