Journal article
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
The journal of clinical endocrinology and metabolism, Vol.89(12), pp.6168-6172
12/01/2004
DOI: 10.1210/jc.2004-1414
PMID: 15579773
Abstract
Abstract 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.
Details
- Title: Subtitle
- 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
- Creators
- Anjli Venkateswaran - The Ohio State Biochemistry Program (A.V., S.M.J.), Columbus, Ohio 43210, Department of Physiology and Cell Biology (A.V., D.K.M., S.M.J.), Columbus, Ohio 43210Derek K Marsee - Department of Physiology and Cell Biology (A.V., D.K.M., S.M.J.), Columbus, Ohio 43210, Medical Scientist Program (D.K.M.), The Ohio State University, Columbus, Ohio 43210Steven H Green - Department of Biological Sciences (S.H.G.), University of Iowa, Iowa City, Iowa 52242-1324Sissy M Jhiang - The Ohio State Biochemistry Program (A.V., S.M.J.), Columbus, Ohio 43210, Department of Physiology and Cell Biology (A.V., D.K.M., S.M.J.), Columbus, Ohio 43210
- Resource Type
- Journal article
- Publication Details
- The journal of clinical endocrinology and metabolism, Vol.89(12), pp.6168-6172
- DOI
- 10.1210/jc.2004-1414
- PMID
- 15579773
- NLM abbreviation
- J Clin Endocrinol Metab
- ISSN
- 0021-972X
- eISSN
- 1945-7197
- Language
- English
- Date published
- 12/01/2004
- Academic Unit
- Biology; Otolaryngology
- Record Identifier
- 9984217414002771
Metrics
13 Record Views