Interplay between Rac1b and Sodium Iodide symporter expression in thyroid and breast cancers

• Autor(a) principal: Capinha, Liliana Mónica Santos
• Data de Publicação: 2015
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/61274
• topic: RAC1b; Sodium Iodide Symporter; Thyroid: Breast; Cancer; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

Rac1b, an alternative isoform of the small GTPase RAC1, has recently be shown to be present in thyroid tissue and overexpressed in thyroid cancer cells, particularly in a subset of papillary thyroid carcinomas carrying the activating mutation BRAFV600E that are associated with an unfavorable outcome. On the other hand, RAC1 seems to be involved in the upregulation of NIS, the glycoprotein responsible for iodide uptake that allows the use of 131 I as a diagnostic and therapeutic tool, in thyroid cancer. However, NIS expression levels and iodine uptake in thyroid cancer cells are reduced when compared to normal tissue. Also, B-Raf V600E mutation has been shown to correlate with a lower expression of NIS. RAC1b overexpression has also been documented in breast cancer. This hyperactivatable variant was shown to be able to compete with and inhibit RAC1 endogenous activity in several signaling pathways. Breast carcinomas also express NIS but at levels too low to warrant treatment with 131I. Thus, in order to understand the regulatory mechanisms of NIS expression we aimed to evaluate the balance of RAC1/1b effect in NIS mRNA expression in follicular cell derived thyroid tumor samples, as well as, in a cell line derived from normal thyroid and in breast cancer cell lines. Understanding the necessary switch to increase NIS expression in cancer cells, would open a new window of opportunity to fight thyroid tumor resistance to radioiodine therapy and develop and possible treatment by the radiodide uptake therapy in breast cancer in a selective way.