Abstract 235: Desmocollin 2 (DSC2), identified by CAST method, is associated with intestinal phenotype of gastric cancer

Abstract

Abstract Gastric cancer (GC) is one of the most common human cancers. Identification of novel genes encoding secreted or transmembrane proteins expressed specifically in GC is important for the development of ideal biomarkers for cancer diagnosis and therapeutics. In the present study, we tried to identify genes encoding cell surface and secretory proteins in GC using Escherichia coli ampicillin secretion trap (CAST) method. CAST libraries were generated from two GC cell lines, MKN-1 and MKN-28. Ampicillin-resistant 1,440 colonies from each library were sequenced and these sequences were compared to the public databases using BLAST (NCBI). Many genes encoding secreted and transmembrane proteins including some known genes were identified. Quantitative RT-PCR was performed to confirm the overexpression of the candidate genes in GC, and the expressions of several genes are narrowly restricted in GC. Among these genes, we focused on the desmosomal cadherin desmocollin 2 (DSC2). DSC2 is ubiquitously expressed in several normal tissues where desmosomes exist. In cancers, the reduction of DSC2 in sporadic colorectal cancer is reported as desmocollin switching. It is also known that the homeodomain transcription factors Cdx1 and Cdx2 regulate DSC2 expression in colon cancer cells. Quantitative RT-PCR analyses with 14 kinds of normal tissues and 9 GC cases showed that DSC2 is highly expressed in GCs. In normal tissues, the expression was seen in the heart and pancreas at the lower levels, but not in the stomach. Overexpression of DSC2 was observed in 13 (31%) of 41 GC cases. Immunohistochemical analyses revealed that DSC2 was preferentially expressed in the cases with mucosal or submucosal invasion. DSC2 expression was significantly associated with the well differentiated cases. There were no correlations between DSC2 expression and lymph node metastasis, pathological stage, or overall survival. Additionally, DSC2 was significantly associated in GCs positive for MUC2 and CDX2. Cell invasion assay and MTT assay revealed that knockdown for DSC2 of GC cell lines by siRNA did not inhibit either cell growth or invasion ability. These findings suggest that DSC2 is involved in GC with intestinal differentiation. DSC2 is a good biomarker of intestinal type GC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 235.