ANALYSISOF THE CREB3L1 TRANSCRIPTION FACTOR IN NORLMAL THYROID CELLS AND BRAF(V600E)EXPRESSING THYROID CELL LINES

CREB3L1 is a transcription factor (TF), member of the CREB3 subfamily,that was first described as involved in the unfolded protein response (UPR),and is activated through regulated intramembrane proteolysis. In some tissues CREB3L1participates in cell differentiation processes regulating the expression oftissue specific proteins, as well as proteins involved in the secretory pathway(transport factors). Moreover, CREB3L1 was described as a tumor suppressorfactor by some authors while others postulated this TF as pro-tumorigenic insome specific types of cancer. We have previously described that CREB3L1regulates the expression of proteins that contribute to the thyroid specificactivity. However, the role of CREB3L1 in the differentiation process ofthyroid cells is still unknown. Here, we aimed to study the role of CREB3L1 in normalthyroid cells by analyzing the effect of CREB3L1 overexpression on NIS proteinlevels, and thyroid functionality by a radioactive iodine uptake assay. On theother hand, we analyzed the expression levels of CREB3L1 in thyroid cells expressingBRAF(V600E), a very common mutated kinase in some types of thyroid cancers. Ourresults show that CREB3L1 overexpression was able to increase NIS proteinlevels and iodine uptake in wt thyroid cells. In an oncogenic context, CREB3L1 proteinlevels seems to decrease after 7 days of BRAF(V600E) expression, whereas theactivation of this TF increases after 3 days of the oncogene expression. Thiscould suggest a dual role for CREB3L1 in which this TF could regulate NIS andthyroid functionality under normal conditions, and in an oncogenic context(where NIS is depleted)...a terminar

Keywords: CREB3L1, NIS, BRAF(V600E).