Overexpression of small ubiquitin-related modifier-1 and sumoylated Mdm2 in oral squamous cell carcinoma: possible involvement in tumor proliferation and prognosis.

The purpose of this research was to identify a molecular clue to tumor proliferation in oral squamous cell carcinoma (SCC) and to test the value as a predictive marker for prognosis. In cDNA array analysis, small ubiquitin-related modifier-1 (SUMO-1) was expressed at much higher levels in oral SCC tissue and oral SCC cell lines than normal oral epithelium. The result was confirmed by RT-PCR analysis and Western blot analysis. Transfection of the anti-SUMO-1 antisense oligonucleotide to oral SCC cells significantly reduced proliferation of the cells. Immunoprecipitation and Western blot analyses revealed that the oncoprotein Mdm2 was present predominantly as a form of SUMO-1 congestion (sumoylation) rather than as a non-sumoylated form in both oral SCC tissues and cell lines. Immunohistological analysis revealed that patients who showed coexpression of SUMO-1 and Mdm2 experienced more frequently local recurrence after initial treatments. Multivariate analysis confirmed that the dual-high expression of SUMO-1 and Mdm2 was an independent factor for local failure. These result suggested that overexpression of Mdm2 caused by overexpression of SUMO-1 may be involved in tumor aggressiveness even in patients with early stage oral SCC. SUMO-1 may be useful as a novel target for therapy in oral SCC as well as a clinical indicator for tumor recurrence together with Mdm2.