Endocrine Abstracts

Thyroid cancer remains the most common endocrine malignancy worldwide and its incidence and mortality has increased steadily over the last four decades. In general terms it has a good outcome, however, some patients develop aggressive forms of thyroid cancer that are untreatable and the molecular bases are poorly understood. These aggressive forms have lost NIS (Na/I Symporter) function, one of the most important hallmarks during thyroid cancer progression as it leads to radio...

Thyroid cancer remains the most common endocrine malignancy worldwide and its incidence and mortality has increased steadily over the last four decades. In general terms it has a good outcome, however, some patients develop aggressive forms of thyroid cancer that are untreatable and the molecular bases are poorly understood. These aggressive forms have lost NIS (Na/I Symporter) function, one of the most important hallmarks during thyroid cancer progression as it leads to radio...

The presence of differentiated follicular thyroid cells in thyroid cancer is critical for the antitumor response to radioactive iodide treatment, and loss of the differentiated phenotype is a key hallmark of iodide-refractory metastatic disease. Thus, one of the objective of our laboratory is to study the signals and molecular mechanisms involved in thyroid differentiation in cancer. Among genes responsible of thyroid differentiated phenotype are the transcription factor PAX8 ...

Cell differentiation occurs as a result of the concerted activation of multiple signalling pathways in response to environmental stimuli. We have stu died the role elicited by several growth factors and oncogenes in the control of Sodium/Iodide Symporter (NIS) gene expression, a thyroid differentiation marker. Our results have shown that IGF1/PI3K and TGFbeta/Smads inhibit NIS gene transcription induced by TSH/cAMP, a mechanism mediated by the inhibition of Pax8 binding to NIS...

Thyroid cancer derived from follicular cells is the most frequently endocrine malignancy with an increasing rate of incidence. The identification of new molecules involved in the pathogenesis of these tumors is necessary in order to use it as a novel targets for a better diagnostic and therapy. Recently, the RNA networks emerge as fundamental in the control of gene expression, achieving a strong interest the microRNAs (miRNAs). Our RNA-Seq study together with the analysis of T...

The oncofoetal miRNA-binding protein LIN28B plays an important role in differentiation and cancer progression. Lin28B induces epithelial-mesenchymal transition, and it is considered as a bad prognostic marker in several tumours. The aim of this work was to study the effect and regulation of LIN28B on the thyroid cancer progression process. In a first approximation a miRNA targets computational predictions were performed with miRanda algorithm and we found that among others the...

Anaplastic thyroid carcinomas (ATC) are characterised by a poor prognosis, due to a highly proliferative, metastatic and undifferentiated state. Follicular thyroid cells undergo epithelial to mesenchymal transition (EMT) by the upregulation of TGFβ pathway. Interestingly, in many epithelial cancer types a correlation between high levels of SIX1 expression and TGFβ signaling has been described.Objective: Study the role of SIX1 homeoprotein in th...

Sox9 is a transcription factor of the HMG box DNA binding family involved in chondrocyte differentiation, sexual determination and the development of endoderm-derived-organs. Preliminary results from our laboratory have shown that Sox9 is expressed in the thyroid gland and its regulation is under the control of TSH and TGFβ. In this work we studied the role of Sox9 in the thyroid cells differentiation and its relationship with the other thyroid transcription factors, main...

The transcription factor Sox9 is a member of the HMG-box-DNA binding family essential for chondrocyte differentiation, sexual determination, and the maintenance of the stem/progenitor cells in several tissues. Furthermore, Sox9 is involved in the development of endoderm-derived-organs. Owing to the endodermic origin of the thyroid, we proposed to study the expression of Sox9 in thyroid follicular cells and its regulation by TSH and TGFβ, two main factors involved in thyro...

Undifferentiated thyroid carcinomas are extremely aggressive and currently lack effective treatment. Aberrant RAS-ERK signaling, triggered mainly by BRAF and RAS mutations, is responsible for the occurrence and progression of most thyroid carcinomas, which led to the clinical use of small kinase inhibitors targeting kinases of the pathway. The results were disappointing, because of the emergence of resistance and high-associated toxicity. A more specific approach, targeting si...