Kyoung Hyun Yu1, Hyewon Youn2, Myung Geun Song1, Dong Soo Lee3, June-Key Chung1. 1. 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 ; Department of Tumor Biology, Seoul National University College of Medicine, Seoul, Korea ; Laboratory of Molecular Imaging and Therapy, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. 2. 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 ; Laboratory of Molecular Imaging and Therapy, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea ; Cancer Imaging Center, Seoul National University Cancer Hospital, Seoul, Korea. 3. 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 ; Department 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 (125)I 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, (125)I 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 (125)I efflux rate by tanespimycin in the normal rat thyroid cells might be attributable to reduced PDS gene expression.
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 (125)I 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, (125)I 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 humancancer cells, and the reduction in the (125)I efflux rate by tanespimycin in the normal rat thyroid cells might be attributable to reduced PDS gene expression.
Entities:
Keywords:
Pendrin; Radioiodine therapy; Sodium-iodide symporter; Tanespimycin (17-AAG); Thyroid cancer
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