Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8477297 | Molecular and Cellular Endocrinology | 2013 | 14 Pages |
Abstract
Loss of sodium-iodide symporter (NIS) expression in thyroid tumour cells primarily caused by constitutive MAPK pathway activation is often refractory to small molecule MAPK inhibitors. Suggested mechanisms are rebound MAPK signalling and activation of alternative signalling pathways. Here we provide evidence that failure to recover down-regulated NIS by MEK inhibition is not specific to tumour cells. NIS mRNA levels remained repressed in TSH-stimulated primary thyroid cells co-treated with epidermal growth factor (EGF) and pan-MEK inhibitor U0126 in the presence of 5% fetal bovine serum or, independently of serum, in 3D cultured thyroid follicles. This led to inhibited iodide transport and iodination. In contrast, U0126 restituted thyroglobulin synthesis in EGF-treated follicular cells. Serum potentiated TSH-stimulated NIS expression in 2D culture. U0126 blocked down-regulation of NIS only in serum-starved cells with a diminished TSH response. Together, this suggests that morphogenetic signals modify the expression of NIS and recovery response to MEK inhibition.
Keywords
EGFU0126LY294002IGF-1PTCTSHMEK1/2 inhibitorFBSPI3KERK1/2MAPKMAPK kinaseNiSTGF-betapotential differenceinsulin-like growth factor-1epithelial to mesenchymal transitiontransforming growth factor-betaEMTThyroidThyroglobulinIodide transportTERsodium iodide symporterpapillary thyroid cancerfetal bovine serumepidermal growth factorphosphoinositide-3-kinaseMEKTransepithelial resistanceMEK inhibitorPI3K inhibitormitogen-activated protein kinase
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Cell Biology
Authors
Camilla Ingeson-Carlsson, Mikael Nilsson,