Abstract

<div>Abstract<p><b>Purpose:</b> 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.</p><p><b>Experimental Design:</b> 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 <i>CD99</i> 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.</p><p><b>Results:</b> 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 (<i>P</i> < 0.05). In addition, most of the gastric adenocarcinoma cases with CD99 down-regulation had reduced expression of SP1 (47 of 103, 45.6%; <i>P</i> < 0.01). This relationship between CD99 and SP1 was consolidated by using SP1 small interfering RNA transfection experiment and <i>CD99</i> promoter luciferase assay. Furthermore, we showed that CD99 down-regulation was associated with proliferation and migration in gastric carcinoma cell line.</p><p><b>Conclusion:</b> These observations suggest that CD99 down-regulation is a critical event in the progression of gastric adenocarcinoma, and <i>CD99</i> promoter methylation, <i>CD99</i> LOH, and SP1 down-regulation were responsible for the down-regulation of CD99.</p></div>

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