Activation of human cancer/testis antigen gene, XAGE-1, in tumor cells is correlated with CpG island hypomethylation

Authors
Jun Hee LimSang-Pyo KimEdward GabrielsonYong Bok ParkJong-Wook ParkTaeg Kyu Kwon
Department
Dept. of Immunology (면역학); Dept. of Pathology (병리학)
Issue Date
2005
Citation
International Journal of Cancer, Vol.116(2) : 200-206, 2005
ISSN
0020-7136
Abstract
Expression of the XAGE-1 antigen is restricted to germ cells of the testis and a variety of neoplastic tissues. To date, the molecular mechanism for regulating expression of this cancer/testis antigen gene has been unknown. To evaluate methylation as a potential mechanism for regulating expression of this gene, we first corre- lated gene methylation status (measured by sequencing of bisul- fide-modified DNA and COBRA) to expression of XAGE-1 mRNA in normal and cancerous cells. This analysis revealed dense meth- ylation of the CpG island in the XAGE-1 gene promoter for the normal and cancerous cells that do not express this gene but loss of this methylation in normal testis, cancer cell lines and the pri- mary gastric cancers where the gene is highly expressed. Further supporting the role of methylation in regulating expression of XAGE-1 were observations that treatment of 2 heavily methylated cell lines, SNU620 and HT29, with 5 0 -aza-deoxycytidine resulted in demethylation of XAGE-1 promoter and corresponding expres- sion of this gene. Finally, we cloned various segments of the CpG- rich XAGE-1 gene promoter linked to a luciferase reporter con- struct and transiently transfected this construct into HCT116 cells. These experiments confirmed transcriptional regulatory activity for the promoter region that incorporates the CpG island and demonstrated that in vitro methylation of this island results in loss of promoter activity. Collectively, these studies indicate that XAGE-1 expression in normal and cancerous tissues is regulated by methylation of the CpG island in the gene promoter. ' 2005 Wiley-Liss, Inc. Key words: XAGE-1; DNA methylation; cancer/testis antigen; promoter; CpG island
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/34840
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
Keimyung Author(s)
박종욱; 권택규; 김상표
Full Text
https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.21007
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