ONCOGENOMICS UbcH10 expression may be a useful tool in the prognosis of ovarian carcinomas MT Berlingieri 1 , P Pallante 1 , M Guida 2 , C Nappi 2 , V Masciullo 3 , G Scambia 3 , A Ferraro 4 , V Leone 4 , A Sboner 5 , M Barbareschi 6 , A Ferro 6 , G Troncone 7 and A Fusco 1,4 1 Dipartimento di Biologia e Patologia Cellulare e Molecolare c/o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facolta`di Medicina e Chirurgia di Napoli, Universita` degli Studi di Napoli ‘Federico II’, Naples, Italy; 2 Dipartimento di Ginecologia e Ostetricia, e Fisiopatologia della Riproduzione Umana, Facolta` di Medicina e Chirurgia di Napoli, Universita` degli Studi di Napoli ‘Federico II’, Naples, Italy; 3 Istituto di Clinica Ostetrica e Ginecologica, Universita` Cattolica del S.Cuore, Rome, Italy; 4 NOGEC (Naples Oncogenomic Center)-CEINGE, Biotecnologie Avanzate-Napoli, & SEMM – European School of Molecular Medicine – Naples Site, Naples, Italy; 5 Bioinformatics – SRA Division ITC-irst, Centre for Scientific and Technological Research, Povo (Trento), Italy; 6 U.O. Anatomia Patologica Ospedale S. Chiara Largo Medaglie d’Oro Trento, Italy and 7 Dipartimento di Anatomia Patologica e Citopatologia, Facolta` di Medicina e Chirurgia, Universita` di Napoli ‘Federico II’, Naples, Italy The UbcH10 gene codes for a protein that belongs to the ubiquitin-conjugating enzyme family. Previous studies of our group suggest UbcH10 expression as a valid indicator of the proliferative and aggressive status of thyroid carcinomas. Therefore, to better understand the process of ovarian carcinogenesis, and to look for possible tools to be used as prognostic markers in these neoplasias, we decided to extend the analysis of the UbcH10 expression to the ovarian neoplastic disease. We found that the UbcH10 gene was upregulated in some ovarian carcinoma cell lines analysed. Then, immunohistochemical studies demonstrate that UbcH10 expression significantly corre- lates with the tumor grade and the undifferentiated histotype of the ovarian carcinomas. Furthermore, a significant relationship between UbcH10 expression and overall survival was observed. Finally, the block of UbcH10 protein synthesis by RNA interference inhibited the growth of ovarian carcinoma cell lines, suggesting a role of UbcH10 overexpression in ovarian carcinogenesis. Therefore, all these data taken together suggest the possibility to use UbcH10 detection as a marker for the diagnosis and prognosis of these neoplastic diseases and open the perspective of a therapy of some ovarian carcinomas based on the suppression of the UbcH10 synthesis and/or function. Oncogene (2007) 26, 2136–2140. doi:10.1038/sj.onc.1210010; published online 2 October 2006 Keywords: UbcH10; ovarian; carcinomas; immunohis- tochemistry Ovarian carcinomas have a great impact in human pathology, in fact ovarian cancer is the leading cause of death from gynecological neoplasias and the fifth most common cancer among women worldwide (Ozols et al., 2004; Jemal et al., 2005). Research aimed to determine the specific genes involved in the development of ovarian cancers would help to understand how normal ovarian epithelial cells escape regulation of proliferation, apoptosis and sene- scence. It has been already (Welcsh and King, 2001) determined that approximately 10% of ovarian cancers arises in women who have inherited mutations in cancer- susceptibility genes such as BRCA1, BRCA2 and other DNA repair genes. Conversely, the vast majority of ovarian cancers are sporadic, presumably resulting from the accumulation of genetic damage over lifetime. Several genes involved in ovarian carcinogenesis have been identified, most notably the p53 tumor suppressor (Feki and Irminger-Finger, 2004). Recently in our laboratory, by a microarray gene expression profiling, we found a gene, UbcH10, that was upregulated in thyroid anaplastic carcinoma samples vs the normal thyroid tissues, suggesting a correlation with the malignant progression (Pallante et al., 2005). A high expression of UbcH10 has also been found in carcino- mas of different anatomic origin (Wagner et al., 2004). The UbcH10 gene belongs to the E2 gene family and codes for a protein of 19.6 kDa that is involved in the ubiquitin-dependent proteolysis. In this path- way, ubiquitin-conjugating enzyme (E2), together with ubiquitin ligase (E3), transfers ubiquitin to specific substrate proteins (Hershko and Ciechanover, 1998; Joazeiro and Weissman, 2000). The aim of our work was to investigate whether the UbcH10 expression might be a new useful indicator for the diagnosis and prognosis of ovarian cancer. Therefore, we evaluated the expression of UbcH10 by reverse transcription–polymerase chain reaction (RT–PCR) and Western blot in ovarian carcinoma cell lines in comparison with the normal ovarian tissue. All Received 29 June 2006; revised 27 July 2006; accepted 7 August 2006; published online 2 October 2006 Correspondence: Professor A Fusco, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facolta` di Medicina e Chirurgia, Universita` degli Studi di Napoli ‘Federico II’ and NOGEC (Naples Oncogenomic Center)-CEINGE, Biotecnologie Avanzate-Naples, & SEMM – European School of Molecular Medicine – Naples Site, via Pansini 5, 80131 Napoli, Italy. E-mail: afusco@napoli.com Oncogene (2007) 26, 2136–2140 & 2007 Nature Publishing Group All rights reserved 0950-9232/07 $30.00 www.nature.com/onc ONCOGENOMICS