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Endocrine Abstracts (2012) 29 S1.2

ICEECE2012 Symposia Molecular mechanisms of differentiated thyroid cancer (3 abstracts)

Correlation between the BRAF V600E mutation, TGFβ pathway and tumour invasiveness in papillary thyroid carcinomas

G. Riesco-Eizaguirre 1 & P. Santisteban 2

1Hospital La Paz Biomedical Research Institute (IDIPAZ), Madrid, Spain; 2Biomedical Research Institute, CSIC-UAM, Madrid, Spain.

The V600E mutation of BRAF oncogene is one of the most frequent genetic events in thyroid cancer, particularly in papillary thyroid carcinomas (PTC) and in some anaplastic carcinomas that derive from preexisting PTC. It has been associated with advanced clinical stages, extrathyroidal extension, and a high risk of recurrences, particularly those that have lost the ability to accumulate iodide, a property mediated by the sodium iodide symporter (NIS).

Our previous data have shown that BRAFV600E promotes NIS functional repression in thyroid cells and that BRAF-positive tumors exhibit a significantly reduced NIS expression. In addition this oncogene promotes cell migration and invasion. Its mechanism of action is mediated by the MEK-ERK pathway, although MEK inhibition does not fully rescue BRAF-induced NIS repression. We have shown that the mechanism through which BRAF induces NIS repression and promotes epithelial to mesenchimal transition and invasion is based on the operation of an autocrine TGFβ loop.

The role of TGBβ as oncogenic factor is gaining increasing importance. We have analyzed its role in a panel of thyroid cancer cells lines harbouring the main genetic mutations described so far in thyroid cancer. Thyroid cancer cells were classified in two groups depending on whether TGFβ had an oncogenic response or not. In addition preliminary results show that a high TGFβ-Smad pathway activity is present in the most aggressive forms of human thyroid cancer, including well- differentiated carcinomas with radioiodide-refractory metastatic disease, poorly differentiated and anaplastic carcinomas. We suggest that TGFβ is an oncogenic factor in advanced thyroid cancer.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported by Grants BFU 2010-16025, RD06/0020/0060 (FIS, ISCIII) and S2011-BMD2328 from Comunidad Madrid (Spain).

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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