- Effects of alpha-lipoic Acid on Differentiation of Thyroid Cancer Cells.
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Won Gu Kim, Doo Hee Han, Hyun Jeung Choi, Eui Young Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim
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J Korean Endocr Soc. 2010;25(1):28-36. Published online March 1, 2010
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DOI: https://doi.org/10.3803/jkes.2010.25.1.28
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- BACKGROUND
Induction of re-differentiation is necessary for the proper treatment of patients with recurrent or metastatic differentiated thyroid cancer (DTC) because cancer cells show de-differentiation in about 30% of these patients. In this study, we evaluated the expression of thyroid specific genes after treatment with various agents to induce re-differentiation in the follicular thyroid cancer cell line FTC-133. METHODS: FTC-133 cells were treated with U0126, LY294002, trichostatin A, retinoic acid (RA), 5'-azacytidine and alpha-lipoic acid (ALA). We evaluated mRNA expression of thyroid specific genes, thyroglobulin (Tg), sodium iodine symporter (NIS), PAX-8 and TTF-1 by reverse transcriptase polymerase chain reaction (PCR). Quantified expression of Tg mRNA was also evaluated by real-time PCR. RESULTS: The expression of Tg mRNA increased after 48 h of treatment with 0.1 uM RA and the expression of Tg mRNA and TTF-1 mRNA increased after 48-72 h of treatment with ALA (10~100 uM). There was no change in thyroid specific gene expression by the other agents. Increased expression of Tg mRNA was confirmed by real-time PCR (1.3 times by 10 uM ALA and 3.6 times by 100 uM ALA). There was no basal NIS mRNA expression in FTC-133 cells and none of the tested agents induced expression of NIS mRNA. There was no change in phosphorylation of AMPK1-alpha after ALA treatment of FTC-133 cells. CONCLUSION: ALA increases mRNA expression of Tg and TTF-1 of FTC-133 thyroid cancer cells and these effects are not mediated by activation of AMP kinase. The finding that ALA could be a potential re-differentiation inducing agent in thyroid cancer cells is novel. Further studies are needed to elucidate the mechanism of induction of re-differentiation. Furthermore, the effect of ALA on NIS expression and on iodine uptake should be evaluated using diverse thyroid cancer cell lines.
- Effects of Peroxisome Proliferator-Activated Receptor (PPAR) Delta on the Growth and Invasion of a Thyroid Cancer Cell Line.
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Won Gu Kim, Hyun Jeung Choi, Eui Young Kim, Tae Yong Kim, Won Bae Kim, Seong Chul Kim, Young Kee Shong
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J Korean Endocr Soc. 2009;24(1):25-32. Published online March 1, 2009
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DOI: https://doi.org/10.3803/jkes.2009.24.1.25
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Abstract
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- BACKGROUND
Peroxisome proliferator-activated receptor delta (PPAR-delta) is a ligand-activated nuclear transcription factor that is associated with many diseases, such as diabetes, obesity, metabolic syndrome, and cancer. However, the function of PPAR-delta is controversial in carcinogenesis since its ligands may inhibit or promote the growth of cancer cells. The purpose of this study was to determine the effect of GW501516, the specific agonist of PPAR-delta, in the growth and invasiveness of thyroid cancer cell lines by modulation of the target genes, ANGPTL-4 and MCP-1. METHODS: Three kinds of human cancer cell lines, FRO (thyroid anaplastic carcinoma), NPA (melanoma), and ARO (colon cancer) were treated with GW501516 in serum-free media. Cell viability was assayed using a colorimetric cell counting kit-8 assay. The changes in the level of expression of PPAR-delta and its target genes, angiopoietin-like protein-4 (ANGPTL-4) and monocyte chemotactic protein-1 (MCP-1), were determined by RT-PCR analysis and invasiveness was assessed by a cell invasion assay kit. RESULTS: GW501516 inhibited the cell growth of cancer cell lines in a dose-dependent manner and modulated the stimulation of ANGPTL-4, as well as inhibition of MCP-1. These effects were more prominent in NPA and ARO, but less effective in the thyroid cancer cell line, which had higher PPAR-delta and lower ANGPTL-4 mRNA levels. The inhibitory effects of GW501516 on cancer invasiveness had a similar pattern. CONCLUSION: The activation of PPAR-delta by GW501516 reduced the cell growth and invasiveness of the thyroid cancer cell line. This effect of GW501516 was associated with a stimulatory effect of ANGPTL4 and an inhibitory effect of MCP-1 in cancer cell lines. GW501516 was less effective in the thyroid cancer cell line, which had a low basal ANGPTL-4 mRNA level. The findings of our study serve as an impetus for further studies to elucidate the precise role of ANGPTL-4 and PPAR-delta in carcinogenesis.
- Effects of Simvastatin on the Growth and Invasion of Anaplastic Thyroid Cancer Cells Lines.
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Hyun Jeung Choi, Tae Yong Kim, Eui Young Kim, Won Gu Kim, Won Bae Kim, Young Kee Shong
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J Korean Endocr Soc. 2008;23(4):238-244. Published online August 1, 2008
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DOI: https://doi.org/10.3803/jkes.2008.23.4.238
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Abstract
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- BACKGROUND
Anaplastic thyroid carcinoma has grave prognosis with most patient dying within 6 months of diagnosis. 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have been reported to have an anticancer effect in experimental and clinical studies. In this study, we investigated the effect of HMG-CoA reductase inhibitors on cell growth, invasiveness, adherence and signal transduction to evaluate the possibility of simvastatin as an agent for treatment of thyroid cancer. METHODS: The viability of simvastatin treated 3 thyroid cancer cell lines (FRO, WRO, and ARO) were determined. We evaluated the cell migration, anchorage-independent growth and invasion ability in anaplastic thyroid cell line. The expression and phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regurated kinase (ERK) were determined by immunoblot analysis. RESULTS: Three thyroid cancer cell lines showed concentration dependent decrease of viability after treatment with 100~200 mM of simvastatin. Anaplastic ARO cell line showed the most predominant decrease in viability. In ARO cell lines, cell migration was decreased by concentration dependent manner after treatment with simvastatin (concentration > or = 5 mM). Anchorage independent colony formation also decreased after simvastatin (> or = 10 mM). Finally, immunoblot analysis revealed that the phosphorylation status of FAK and ERK decreased in time dependent manner following treatment with 10 mM of simvastatin. CONCLUSION: The results of this study suggest that simvstatin exerts a favorable effect on the progression and metastasis of thyroid cancer. However, further studies are needed to elucidate the related mechanisms and signal transductions prior to its therapeutic application.
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Citations
Citations to this article as recorded by  - The Effect of Atorvastatin and Simvastatin on NIS Expression of the TPC-1 Cell under the Therapeutic Blood Concentrations
Tae Kyoon Kim, Hye Sook Jung, Chang Shin Yoon, Jung Hae Ko, Hae Jung Jun, Min Jung Kwon, Sun Hee Lee, Mi Kyung Kim, Jeong Hyun Park
Endocrinology and Metabolism.2010; 25(3): 192. CrossRef
- CAG Repeats in the Androgen Receptor Polymorphism do not Correlate with Thyrotoxic Periodic Paralysis.
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Won Gu Kim, Tae Yong Kim, Jung Min Kim, Yoon Soo Rhee, Hyun Jeung Choi, Won Bae Kim, Young Kee Shong
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J Korean Endocr Soc. 2008;23(2):117-122. Published online April 1, 2008
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DOI: https://doi.org/10.3803/jkes.2008.23.2.117
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1,763
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Abstract
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- BACKGROUND
Thyrotoxic periodic paralysis (TPP) occurs mostly in males, but no studies have addressed the role of androgen in the disease. Hyperinsulinemia can precipitate acute paralysis in TPP patients. CAG repeats in the androgen receptor (AR), an X-linked gene, correlate with serum insulin levels. AIM: To evaluate whether CAG repeats in the AR gene might predict the susceptibility to TPP in Korean male Graves' patients. METHODS: We evaluated CAG repeat length in a series of 33 male TPP patients and 48 control patients by direct sequencing of the PCR product of the AR promoter site. Control patients were male Graves' patients without a history of paralysis. RESULTS: The CAG repeat length varied from 15 to 34 (median of 23). The upper quartile of CAG length was equal to or above 26 repeats (long AR). The distribution of long AR was 0.30 in TPP and 0.15 in control patients, respectively (odds ratio, 2.51; 95% confidence interval, 0.92~6.85; P = 0.09). CONCLUSION: AR gene polymorphisms may not confer genetic susceptibility to TPP in Korean male patients with Graves' disease.
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Citations
Citations to this article as recorded by - Contributions of CAG repeat length in the androgen receptor gene and androgen profiles to premature pubarche in Korean girls
Min Jae Kang, Jeong Seon Lee, Hwa Young Kim, Hae Woon Jung, Young Ah Lee, Sun Hee Lee, Ji-Young Seo, Jae Hyun Kim, Hye Rim Chung, Se Young Kim, Choong Ho Shin, Sei Won Yang
Endocrine Journal.2017; 64(1): 91. CrossRef - Thyrotoxic Periodic Paralysis and Polymorphisms of the ADRB2, AR, and GABRA3 Genes in Men with Graves Disease
Suyeon Park, Tae Yong Kim, Soyoung Sim, Seonhee Lim, Mijin Kim, Hyemi Kwon, Min Ji Jeon, Won Gu Kim, Young Kee Shong, Won Bae Kim
Endocrinology and Metabolism.2016; 31(1): 142. CrossRef - Androgen Receptor Gene CAG Repeat Polymorphism and Effect of Testosterone Therapy in Hypogonadal Men in Korea
Min Joo Kim, Jin Taek Kim, Sun Wook Cho, Sang Wan Kim, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim
Endocrinology and Metabolism.2011; 26(3): 225. CrossRef
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