Guerriero, Eliana (2009) UbcH10 is useful in the diagnosis and prognosis of human neoplasms. [Tesi di dottorato] (Unpublished)
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|Item Type:||Tesi di dottorato|
|Date Deposited:||27 May 2010 14:58|
|Last Modified:||30 Apr 2014 19:39|
The UbcH10 gene belongs to the E2 gene family and encodes for a 19.6 kDa protein involved in ubiquitin-dependent proteolysis. The hybridization of an Affymetrix HG_U95Av2 microarray led us to highlight that this gene is up-regulated by 150 fold in all of the thyroid carcinoma cell lines in comparison to a primary cell culture of normal thyroid origin. To assess the role of UbcH10 in cancer progression, we analyzed its expression and its clinical/pathological relevance in breast and thyroid carcinomas and in lymphoproliferative diseases. In these tumor types, analysis of UbcH10 expression was performed on both cell lines and clinical samples by quantitative RT-PCR, Western blot, immunohistochemistry and flow cytometry. The effect of UbcH10 protein suppression by RNA interference was also evaluated in different tumor cell lines. Consistent data were derived from all tumor types. Deregulated UbcH10 expression was clearly associated to a highly malignant phenotype. Implications were both diagnostic and prognostic: UbcH10 specifically associated with the breast tumors more aggressive expressing ErbB2; UbcH10 specifically marked high grade non-Hodgkin lymphomas; high UbcH10 expression increased the suspicion of malignancy on preoperative thyroid biopsies. In several cell lines suppression of UbcH10 expression affected the neoplastic cell growth potential. All together our results indicate that UbcH10 is a marker of aggressive neoplastic behavior. Assessing its expression on clinical samples may contribute to both cancer diagnosis and prognosis. Moreover, the suppression of its function is to be evaluated as a potential therapeutic tool.
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