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Title: Role of genes differentially expressed in thyroid carcinogenesis
Author: Anania, Maria Chiara
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2012
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Papillary thyroid carcinoma (PTC) is characterized by specific alterations, all converging on the activation of the RTK/RAS/BRAF/MAPK pathway. Even though the identification of these alterations of has provided a great contribution to understanding PTC pathogenesis, the molecular mechanisms underlying its development are not completely elucidated. Gene expression analyses have provided new findings contributing to the dissection of PTC pathogenesis. Despite the numerous gene expression studies, there are few data addressing the role of differentially expressed genes in these tumours. Microarray gene expression profile previously determined m our laboratory identified TIMP3, S100All and CITED1 genes as differentially expressed in PTC versus normal thyroid. In this thesis, we performed functional studies in order to assess their role in PTC. TIMP 3 was found to be downregulated in a consistent fraction of PTC. Functional studies in PTC-derived NIM1 cell line showed that TIMP3 restoration had no effect on growth rate; however, it reduced migration, invasion, anchorage independent growth and in vivo tumourigenicity, supporting a tumour suppressor role in thyroid carcinogenesis. S100A11 was found upregulated in PTC. S100A11 localization and the crosstalk with the EGF/EGFR pathway were analyzed in the PTC-derived Kl cells. The S100A11 silencing in Kl affected cellular anchorage-independent growth, but not proliferation and in vivo tumourigenicity. Co-transfection experiments in NIH3T3 cells showed that SI OOA 11 was able to enhance the transforming capability of the PTC-associated TRK- T3 oncogene. CITED1 was found overexpressed in PTC. Our preliminary experiments involved the analysis of CITED1 expression in a collection of PTC-derived cell lines and the construction CITED1 cDNA expression vectors. Functional studies, such as the investigation of the effect of CITED1 on transforming activity of PTC-associated oncogenes and the effect of its silencing in PTC-derived cell lines, will be performed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available