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Clinical Significance of CD99 Down-Regulation in Gastric Adenocarcinoma

Cited 24 time in Web of Science Cited 25 time in Scopus
Issue Date
2007-05
Publisher
American Association for Cancer Research
Citation
Clin Cancer Res; Vol.13(9); pp.2584-2591
Abstract
Purpose: CD99 is a cell adhesion molecule associated with human tumors. The aim of the present study was to characterize its role in the development and progression of human gastric adenocarcinoma.
Experimental Design: The expression of CD99 was investigated in 283 gastric adenocarcinomas and related lesions and 9 gastric carcinoma cell lines. We also analyzed the methylation status of CD99 gene by using methylation-specific PCR and examined loss of heterozygosity (LOH) of this gene locus by using an intragenic marker. Moreover, we assessed whether SP1, a positive transcription factor for CD99, is expressed in these samples.
Results: We found that the decreased expression of CD99 was strongly associated with poor survival and unfavorable clinicopathologic variables. Promoter region methylation (15 of 89, 16.9%) and LOH (21 of 74, 28.4%) were observed and significantly associated with CD99 down-regulation (P < 0.05). In addition, most of the gastric adenocarcinoma cases with CD99 down-regulation had reduced expression of SP1 (47 of 103, 45.6%; P < 0.01). This relationship between CD99 and SP1 was consolidated by using SP1 small interfering RNA transfection experiment and CD99 promoter luciferase assay. Furthermore, we showed that CD99 down-regulation was associated with proliferation and migration in gastric carcinoma cell line.
Conclusion: These observations suggest that CD99 down-regulation is a critical event in the progression of gastric adenocarcinoma, and CD99 promoter methylation, CD99 LOH, and SP1 down-regulation were responsible for the down-regulation of CD99.
ISSN
1557-3265
1078-0432
Language
English
URI
https://hdl.handle.net/10371/73425
DOI
https://doi.org/10.1158/1078-0432.CCR-06-1785
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College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
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