Over-Expression of Small Ubiquitin-Related Modifier-1 and Sumoylated p53 in Colon Cancer
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ORIGINAL PAPER
Over-Expression of Small Ubiquitin-Related Modifier-1 and Sumoylated p53 in Colon Cancer Hongjie Zhang • Xiaoyi Kuai • Zeyu Ji Zhengyang Li • Ruihua Shi
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Ó Springer Science+Business Media New York 2013
Abstract Here we investigated whether the cellular accumulation of p53 protein caused by over-expression of small ubiquitin-related modifier-1 (SUMO-1) could be used as a predictive marker for prognosis in colon cancer. We detected SUMO-1 and p53 protein levels in 46 cases of colon cancer and adjacent tissues by immunohistochemistry and found that SUMO-1 was expressed at much higher levels in colon cancer compared with that in normal colon tissue. Immunoprecipitation and Western blot analysis revealed that the tumor suppressor p53 was present predominantly in the sumoylated rather than the non-sumoylated form in the colon cancer cell lines. A small interfering RNA targeted to SUMO-1 mRNA sequences was used to observe the levels of the p53 protein. Patients who showed high dual expressions of SUMO-1 and p53 tended to experience metastasis more frequently. These results suggest that the cellular accumulation of p53 protein caused by over-expression of SUMO-1 may be involved in tumor aggressiveness. Multivariate analysis confirmed that the high dual expression of SUMO-1 and p53 was an independent factor for evaluating prognosis. SUMO-1 may be useful as a novel target for therapy in colon cancer as well as a clinical indicator for tumor aggressiveness. Keywords Small ubiquitin-related modifier-1 Sumoylation SUMO-1 p53 Colon cancer Predictive marker Immunohistochemistry Electronic supplementary material The online version of this article (doi:10.1007/s12013-013-9612-x) contains supplementary material, which is available to authorized users. H. Zhang X. Kuai Z. Ji Z. Li R. Shi (&) Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China e-mail: [email protected]
Introduction Etiology of colorectal cancer still remains incompletely clear, its occurrence in the process is a multi-factor, multistep, including oncogenes and tumor suppressor genes abnormalities. Mutations in the p53 gene and cellular accumulation of the p53 protein are common in colorectal cancer [1]. The lack of preventive strategies, early diagnostic tools, and effective therapies to treat colon cancer prompts an urgent need to better understand its pathogenesis at the molecular level. The tumor suppressor p53 is an important regulator in cell growth, differentiation, apoptosis, and in the maintenance of genome integrity [2]. The protein level and function of p53 are tightly regulated by a variety of posttranslational modifications including non-protein modifications like phosphorylation and acetylation and protein modifications such as ubiquitination and sumoylation [1, 3]. Small ubiquitin-related modifier-1 (SUMO-1) is involved in post-translational modifications [4–6]. SUMO-1 is reversibly attached to other proteins in a ubiquitination-like manner. U
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