S-Space College of Medicine/School of Medicine (의과대학/대학원) Preventive Medicine (예방의학전공) Journal Papers (저널논문_예방의학전공)
Clinical significance of CD99 down-regulation in gastric adenocarcinoma
- 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
- American Association for Cancer Research
- Clin Cancer Res 2007;13:2584-91
- Adenocarcinoma/chemistry/genetics/*pathology; Antigens, CD/analysis/*genetics; Cell Adhesion Molecules/analysis/*genetics; DNA Methylation; Down-Regulation; Female; *Gene Expression Regulation, Neoplastic; Humans; *Loss of Heterozygosity; Male; Middle Aged; Promoter Regions, Genetic; Sp1 Transcription Factor/genetics/metabolism; Stomach Neoplasms/chemistry/genetics/*pathology
- 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.
- 1078-0432 (Print)
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