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Clinical significance of CD99 down-regulation in gastric adenocarcinoma

Cited 22 time in Web of Science Cited 24 time in Scopus
Authors
Lee, Jung Hyun; Kim, Seok-Hyung; Wang, Li-Hui; Choi, Yoon-La; Kim, Young Chul; Kim, Jin Hee; Park, Tae Sung; Hong, Yun-Chul; Shin, Young Kee
Issue Date
2007-05-01
Publisher
American Association for Cancer Research
Citation
Clin Cancer Res 2007;13:2584-91
Keywords
Adenocarcinoma/chemistry/genetics/*pathologyAntigens, CD/analysis/*geneticsCell Adhesion Molecules/analysis/*geneticsDNA MethylationDown-RegulationFemale*Gene Expression Regulation, NeoplasticHumans*Loss of HeterozygosityMaleMiddle AgedPromoter Regions, GeneticSp1 Transcription Factor/genetics/metabolismStomach Neoplasms/chemistry/genetics/*pathology
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
1078-0432 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17473187

https://hdl.handle.net/10371/23570
DOI
https://doi.org/10.1158/1078-0432.CCR-06-1785
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College of Medicine/School of Medicine (의과대학/대학원)Preventive Medicine (예방의학전공)Journal Papers (저널논문_예방의학전공)
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