MEK signaling modulates sodium iodide symporter at multiple levels and in a paradoxical manner
| Autor: | Douangsone D. Vadysirisack, Anjli Venkateswaran, Zhaoxia Zhang, Sissy M. Jhiang |
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| Rok vydání: | 2007 |
| Předmět: |
Sodium-iodide symporter
MAPK/ERK pathway Cancer Research medicine.medical_specialty Endocrinology Diabetes and Metabolism MAP Kinase Kinase 1 Thyroid Gland Ouabain Adenoviridae Thyroid carcinoma Endocrinology Internal medicine Cell Line Tumor medicine Animals Iodide transport Protein Kinase Inhibitors health care economics and organizations Flavonoids Mitogen-Activated Protein Kinase Kinases Symporters Chemistry MEK inhibitor Thyroid Iodides Rats medicine.anatomical_structure Oncology Symporter Sodium-Potassium-Exchanging ATPase medicine.drug Signal Transduction |
| Zdroj: | Endocrine-related cancer. 14(2) |
| ISSN: | 1351-0088 |
| Popis: | The Na+/I− symporter (NIS)-mediated iodide uptake is the basis for targeted radioiodine ablation of thyroid cancers. However, NIS-mediated radioiodide uptake (RAIU) activity is often reduced in thyroid cancers. As mitogen activated protein kinase (MAPK) signaling pathway is activated in about 70% of papillary thyroid carcinoma, we investigated whether MEK (MAPK kinase) inhibition will restore NIS protein levels and NIS-mediated RAIU activity in RET/PTC oncogene-transformed thyroid cells. We found that MEK inhibitor PD98059 increased NIS protein levels within 30 min of treatment. However, the increase of NIS protein level was not accompanied with an increase in NIS-mediated RAIU activity, particularly at early time points of PD98059 treatment. PD98059 also decreased RAIU activity mediated by exogenous NIS in non-thyroid cells. The transient decrease of RAIU activity by PD98059 in thyroid cells was not due to decreased NIS cell surface level, decreased NIS binding affinity for I− , or increased iodide efflux. While PD98059 moderately decreased Na+/K+-ATPase activity, ouabain titration indicates that the extent of decrease in Na+/K+-ATPase activity is much greater than the extent of decrease in RAIU activity. Additionally, a decrease of Na+/K+-ATPase activity was not accompanied with a decrease of biotin uptake activity mediated by Na+-dependent multivitamin transporter. Since PD98059 reduced Vmax− I− without decreasing NIS cell surface levels, it is most likely that PD98059 decreases the turnover rate of iodide transport with an yet to be identified mechanism. |
| Databáze: | OpenAIRE |
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