Abstract

Abstract Colorectal cancer is one of the most prevalent tumors in developed countries, and the best characterized cancers with regard to genetic progression of disease. Recent improvement in methods for proteome analysis has offered the possibility of identifying disease-associated protein markers to assist in diagnosis or prognosis, and for selecting potential targets for specific drug therapy. For identification and targeting of tumor-associated marker proteins, the proteome of colorectal adenocarcinoma (CRC) and normal colorectal tissues was analyzed by 2-DE. Inosine monophosphate dehydrogenase type 2 (IMPDH2), a key enzyme of de novo purine nucleotide biosynthesis, was identified by MALDI-TOF/MS and found to be expressed at high rates in the colorectal tumor tissues. We found an increased amount of IMPDH2 mRNA in CRC compared to that observed in the normal colorectal tissues by Northern blot. Real time PCR analysis in both tissues also revealed the higher expression of IMPDH2 mRNA in CRC. Western blot analysis was carried out to confirm the elevated expression of protein level for IMPDH2 in CRC compared with normal tissues. Immunohistochemical studies denoted that tumor tissues showed higher N/C ratio, abnormal shape of gland, and darker staining in glandular area. In addition, using in situ hybridization, it was demonstrated the expression of IMPDH2 in CRC tissues was extremely high in the vicinity of mucosal gland, while IMPDH2 in the normal colorectal tissues was evenly distributed in all tissue area with lower level. These findings suggest that IMPDH2 could be a possible tumor biomarker candidate in CRC tissues. This study was supported by KOSEF grant (R13-2005-012-01003-0) and KRF grants (2006-005-J04203). 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 5558.

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