Nucl Med Mol Imaging.
2012 Dec;46(4):239-246.
The Effect of Tanespimycin (17-AAG) on Radioiodine Accumulation in Sodium-Iodide Symporter Expressing Cells
- Affiliations
-
- 1Department of Nuclear Medicine, Seoul National University College of Medicine, #207-4, Samsung Cancer Research Building, 28 Yeongeon-dong, Jongno-gu, Seoul 110-744, Korea. hwyoun@snu.ac.kr
- 2Department of Tumor Biology, Seoul National University College of Medicine, Seoul, Korea.
- 3Laboratory of Molecular Imaging and Therapy, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
- 4Cancer Imaging Center, Seoul National University Cancer Hospital, Seoul, Korea.
- 5Department of Molecular Medicine and Biopharmaceutical Science, WCU Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
Abstract
- PURPOSE
The heat shock protein 90 inhibitor, tanespimycin, is an anticancer agent known to increase iodine accumulation in normal and cancerous thyroid cells. Iodine accumulation is regulated by membrane proteins such as sodium iodide symporter (NIS) and pendrin (PDS), and thus we attempted to characterize the effects of tanespimycin on those genes.
METHODS
Cells were incubated with tanespimycin in order to evaluate 125I accumulation and efflux ability. Radioiodine uptake and efflux were measured by a gamma counter and normalized by protein amount. RT-PCR were performed to measure the level of gene expression.
RESULTS
After tanespimycin treatment, 125I uptake was increased by ~2.5-fold in FRTL-5, hNIS-ARO, and hNIS-MDA-MB-231 cells, but no changes were detected in the hNIS-HeLa cells. Tanespimycin significantly reduced the radioiodine efflux rate only in the FRTL-5 cells. In the FRTL-5 and hNIS-ARO cells, PDS mRNA levels were markedly reduced; the only other observed alteration in the levels of NIS mRNA after tanespimycin treatment was an observed increase in the hNIS-ARO cells.
CONCLUSIONS
These results indicate that cellular responses against tanespimycin treatment differed between the normal rat thyroid cells and human cancer cells, and the reduction in the 125I efflux rate by tanespimycin in the normal rat thyroid cells might be attributable to reduced PDS gene expression.
Keyword
MeSH Terms
-
Animals
Benzoquinones
Gene Expression
Heat-Shock Proteins
Humans
Iodine
Ion Transport
Lactams, Macrocyclic
Membrane Proteins
Organothiophosphorus Compounds
Rats
RNA, Messenger
Sodium Iodide
Symporters
Thyroid Gland
Thyroid Neoplasms
Benzoquinones
Heat-Shock Proteins
Iodine
Lactams, Macrocyclic
Membrane Proteins
Organothiophosphorus Compounds
RNA, Messenger
Sodium Iodide
Symporters
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Sodium Iodide Symporter (NIS) in the Management of Patients with Thyroid Carcinoma
- Sodium Iodide Symporter and the Radioiodine Treatment of Thyroid Carcinoma
- Radioiodine Therapy in Differentiated Thyroid Cancer: The First Targeted Therapy in Oncology
- RAI Treatment of Distant Metastasis of Thyroid Cancer
- Total Thyroidectomy in the Mouse: the Feasibility Study in the Non-thyroidal Tumor Model Expressing Human Sodium/Iodide Symporter Gene
