Forskolin, 8-Br-3′,5′-Cyclic Adenosine 5′-Monophosphate, and Catalytic Protein Kinase A Expression in the Nucleus Increase Radioiodide Uptake and Sodium/Iodide Symporter Protein Levels in RET/PTC1-Expressing Cells
| Autor: | Anjli Venkateswaran, Sissy M. Jhiang, Derek K. Marsee, Steven H. Green |
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| Rok vydání: | 2004 |
| Předmět: |
Adenosine monophosphate
Sodium-iodide symporter congenital hereditary and neonatal diseases and abnormalities endocrine system medicine.medical_specialty Oncogene Proteins Fusion endocrine system diseases Recombinant Fusion Proteins Endocrinology Diabetes and Metabolism Green Fluorescent Proteins Clinical Biochemistry 8-Bromo Cyclic Adenosine Monophosphate Biochemistry Iodine Radioisotopes chemistry.chemical_compound Endocrinology Internal medicine medicine Colforsin Animals Tissue Distribution Protein kinase A neoplasms Cell Line Transformed Cell Nucleus Forskolin Symporters Kinase Biochemistry (medical) Protein-Tyrosine Kinases Cyclic AMP-Dependent Protein Kinases Rats chemistry Symporter Signal transduction |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 89:6168-6172 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2004-1414 |
| Popis: | RET/PTC1, a thyroid-specific oncogene, has been reported to down-regulate sodium/iodide symporter (NIS) expression and function in vitro and in vivo. Recently, RET/PTC1 has been shown to interfere with TSH signaling at multiple levels in thyroid cells. The objective of this study was to investigate whether RET/PTC1-mediated NIS reduction can be rescued by activating cAMP-protein kinase A (PKA) pathways. We showed that both forskolin and 8-Br-cAMP increase radioiodide uptake and NIS protein in RET/PTC1-expressing cells to the same extent as the parental PC Cl 3 cells. We found that RET/PTC1 decreases nuclear localization of catalytic PKA, and forskolin treatment was able to counteract this RET/PTC1 effect. Furthermore, transient expression of catalytic PKA in the nucleus increased radioiodide uptake and NIS protein in RET/PTC1-expressing cells. Taken together, these studies suggest that RET/PTC1 down-regulates NIS expression by interrupting TSH/cAMP signaling, and this RET/PTC1 effect can be reversed by activating cAMP-PKA pathways. |
| Databáze: | OpenAIRE |
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