The Effect of Tanespimycin (17-AAG) on Radioiodine Accumulation in Sodium-Iodide Symporter Expressing Cells
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ORIGINAL ARTICLE
The Effect of Tanespimycin (17-AAG) on Radioiodine Accumulation in Sodium-Iodide Symporter Expressing Cells Kyoung Hyun Yu & Hyewon Youn & Myung Geun Song & Dong Soo Lee & June-Key Chung
Received: 17 September 2011 / Revised: 4 May 2012 / Accepted: 15 July 2012 / Published online: 15 August 2012 # Korean Society of Nuclear Medicine 2012
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 hNISMDA-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
K. H. Yu : H. Youn (*) : M. G. Song : D. S. Lee : J.-K. Chung (*) Department of Nuclear Medicine, Seoul National University College of Medicine, #207-4, Samsung Cancer Research Building, 28 Yeongeon-dong, Jongno-gu, Seoul 110-744, Korea e-mail: [email protected] e-mail: [email protected]
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. Keywords Thyroid cancer . Radioiodine therapy . Tanespimycin (17-AAG) . Sodium-iodide symporter . Pendrin
Introduction Differentiated thyroid carcinoma is one of the most common endocrine cancers. The current preferred treatments for this cancer are the surgical removal of the thyroid gland and
H. Youn Cancer Imaging Center, Seoul National University Cancer Hospital, Seoul, Korea
K. H. Yu : M. G. Song : J.-K. Chung Department of Tumor Biology, Seoul National University College of Medicine, Seoul, Korea K. H. Yu : H. Youn : M. G. Song : J.-K. Chung Laboratory of Molecular Imaging and Therapy, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
D. S. Lee Department of Molecular Medicine and Biopharmaceutical Science, WCU Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea
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radioiodine therapy [1]. Radioactive iodine therapy has proven to be a very effective treatment for residual and recurrent thyroid cancers,
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