REGULATION OF THE SODIUM/IODIDE SYMPORTER (NIS) BY CREB3L1

TORRES DEMICHELLIS VA; ALVAREZ C; MARTIN M; NICOLA JP; DI GIUSTO P; SAMPIERI L

Paraná

Congreso; 54th Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology; 2018

SAIB

NIS is required for thyroid iodide uptake. Its expression is fundamental for the use of radioiodine in the treatment of thyroid carcinomas. The BRAF(V600E) mutation is the most common genetic alteration in papillary thyroid carcinomas. This oncoprotein confers cancer cells with a more aggressive phenotype and decreased thyrotropin (TSH)-responsiveness. In agreement, BRAF(V600E) mutation correlates with low expression levels of thyroid-specific genes, including NIS. We have described that in thyroid cells, the transcription factor CREB3L1 regulates the expression of transport factors in response to TSH. In addition, in bone cells, CREB3L1 regulates the expression of transport factors as well as the expression of bone-specific genes. However, the function of CREB3L1 in the regulation of thyroid-specific proteins is still unknown. Here, we analyzed the effect of CREB3L1 overexpression on NIS levels and activity (125I uptake assay) in thyroid cells. Our results show that CREB3L1 overexpression increases NIS levels and iodide uptake. Furthermore, we examined CREB3L1 in a BRAF(V600E) inducible system, where NIS levels decrease after the induction of the oncogene. Interestingly, CREB3L1 levels increase after 5 days of BRAF(V600E) induction but then decrease after 7 days. Taken together, our results indicate a dual behavior of CREB3L1 in a normal context and an oncogenic context. But CREB3L1 regulation and its impact on thyroid function remains to be characterized