Expression of SUMO proteins in normal testicular cells and in germ cell tumors

Jennifer L Fathy, Yeshiva University Ellen Dinerman, Yeshiva University Margarita Vigodner, Yeshiva University

Abstract Spermatogenesis is the complex process of gamete formation, including mitosis of spermatogonia, meiosis of spermatocytes, and differentiation of haploid, nonmotile spermatids into motile sperm. Testicular tumors are rare, comprising 2% of all cancers in men; however, testicular cancer is the most common malignancy affecting males aged 20–35 years. SUMO (small ubiquitin-like modifier) proteins were discovered a decade ago based on their homology to ubiquitin. SUMOylation (covalent modification by SUMO of the lysine residue of the target protein) is implicated in numerous cellular events, such as transcription regulation (repression in most cases), cell division, apoptosis, and nuclear-cytoplasmic transport. Several members of the SUMO superfamily (SUMO-1, SUMO-2 and SUMO-3) have been identified and their functions in different tissues were shown to be non-overlapping. Alterations of SUMO conjugation have been implicated in several human diseases, including cancer. SUMO-1 has recently been localized in different testicular cells, but the role this and other SUMO proteins play in the process of normal germ cell maturation and development of testicular cancer remains largely unknown. In this study, using immunofluorescence, immunohistochemistry, Western blot, and tissue microarray analyses, we compared the expression pattern of SUMO-1, SUMO-2, and SUMO-3 in normal testicular cells and in germ cell tumors. The expression and the regulatory pattern of different SUMO proteins in germ and somatic testicular cells varied from each other. In germ cell tumors, we observed several different patterns of SUMO localization, including nuclear, cytoplasmic and negative staining. Our results imply the non-overlapping function of SUMO proteins during spermatogenesis and suggest that sumoylation may play a role in development of testicular cancer. Further studies are aimed at correlating the different patterns of SUMO expression in germ cell tumors with progressive stages of testicular cancer.

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