Regulation of Expression of Sterol Regulatory Element-binding Protein 1 in Thyroid Cancer Cells.

Abstract

Expression of sterol regulatory element-binding protein 1 (SREBP1) is upregulated in thyroid cancer and associated with shorter disease-specific survival. The molecular regulatory mechanisms governing SREBP1 over-expression in thyroid cancer are still unclear. Thyroid cancer cell lines BHT-101 (with the BRAF V600E mutation) and FTC-131 (wild-type for BRAF) were treated with specific inhibitors. The expression of SREBP1 was determined at the mRNA level using quantitative real-time PCR and at the protein level using immunoblotting. Lenvatinib and a MEK inhibitor, selumetinib, suppressed SREBP1 expression in BHT-101 but not FTC-133 cells. Olitigaltin, a galectin-3 inhibitor, decreased SREBP1 expression in a time- and dose-dependent manner in both cells. MK2206, an allosteric AKT inhibitor, did not change SREBP1 expression in either cell line. The galectin-3 inhibitor attenuates SREBP1 expression in thyroid cancer cells, likely independent of AKT phosphorylation. Lenvatinib and selumetinib decreases SREBP1 expression in the BRAF-mutant cell line BHT-101.