Switching from MAPK-dependent to MAPK-independent repression of the sodium-iodide symporter in 2D and 3D cultured normal thyroid cells

Autor: Mikael Nilsson, Camilla Ingeson-Carlsson
Rok vydání: 2013
Předmět:
MAPK/ERK pathway
Sodium-iodide symporter
endocrine system
medicine.medical_specialty
endocrine system diseases
MAP Kinase Signaling System
medicine.medical_treatment
Sus scrofa
Cell Culture Techniques
Thyroid Gland
Gene Expression
Biochemistry
Culture Media
Serum-Free
Endocrinology
Internal medicine
Nitriles
Butadienes
medicine
Animals
Gene Silencing
RNA
Messenger
Iodide transport
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Molecular Biology
Cells
Cultured
health care economics and organizations
Epidermal Growth Factor
Symporters
Chemistry
MEK inhibitor
Thyroid
Biological Transport
Cell Differentiation
Iodides
MAP Kinase Kinase Kinases
Cell biology
medicine.anatomical_structure
Symporter
Thyroglobulin
Protein Processing
Post-Translational
hormones
hormone substitutes
and hormone antagonists
Fetal bovine serum
Zdroj: Molecular and Cellular Endocrinology. 381:241-254
ISSN: 0303-7207
DOI: 10.1016/j.mce.2013.08.006
Popis: 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.
Databáze: OpenAIRE
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