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

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Author(s)
Jun Hee LimSang-Pyo KimEdward GabrielsonYong Bok ParkJong-Wook ParkTaeg Kyu Kwon
Publication Year
2005
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
Department
Dept. of Immunology (면역학)
Dept. of Pathology (병리학)
Publisher
School of Medicine
Citation
International Journal of Cancer, Vol.116(2) : 200-206, 2005
Type
Article
ISSN
0020-7136
DOI
10.1002/ijc.21007
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/34840
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