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

doi:10.3748/wjg.v12.i35.5651

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Colorectal Cancer

World J Gastroenterol. Sep 21, 2006; 12(35): 5651-5657
Published online Sep 21, 2006. doi: 10.3748/wjg.v12.i35.5651

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

Kyung-Hee Kim, Jin-Sung Choi, Il-Jin Kim, Ja-Lok Ku, Jae-Gahb Park

Kyung-Hee Kim, Jin-Sung Choi, Il-Jin Kim, Ja-Lok Ku, Jae-Gahb Park, Laboratory of Cell Biology, Korean Cell Line Bank, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, Korea

Author contributions: All authors contributed equally to the work.

Supported by the Korea Research Foundation Grant, No.KRF-2003-03-E00199

Correspondence to: Ja-Lok Ku, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea. kujalok@snu.ac.kr

Telephone: +82-2-36687919 Fax: +82-2-7420021

Received: May 10, 2006
Revised: June 8, 2006
Accepted: June 14, 2006
Published online: September 21, 2006

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.

Keywords: MAGE-A1; MAGE-A3; Promoter; Hypomethy-lation; Colorectal cancer