The Mechanism of How Endoglin is Positively Regulated by Thyroid Hormone

碩士 === 長庚大學 === 基礎醫學研究所 === 96 === Thyroid hormone (3, 3’, 5-triiodo-L-thyronine, T3)plays an important role in metabolism, growth and development of animals. Most of the effects of thyroid hormone are mediated by thyroid hormone receptors(TRs). TRs function as transcription factors to increase or d...

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Bibliographic Details
Main Authors: Yang Hsiang Lin, 林暘翔
Other Authors: K. H. Lin
Format: Others
Published: 2008
Online Access:http://ndltd.ncl.edu.tw/handle/60859308376323229211
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Summary:碩士 === 長庚大學 === 基礎醫學研究所 === 96 === Thyroid hormone (3, 3’, 5-triiodo-L-thyronine, T3)plays an important role in metabolism, growth and development of animals. Most of the effects of thyroid hormone are mediated by thyroid hormone receptors(TRs). TRs function as transcription factors to increase or decrease levels of gene expression. Our laboratory compared the differentially expressed genes after T3 treatment in a TR over expression hepatoma cell line by oligonucleotide microarray. There were many genes positively regulated by T3, including Endoglin. Since the relationship between T3 and Endoglin has never been reported, we intended to elucidate the role of T3 in regulation of Endoglin and physiological role of Endoglin in hepatoma cell line. The mRNA and protein level of Endoglin were both positively regulated by T3. Similar results were observed in the J7 hepatoma cell line expressing detectable TR protein after T3 application. The protein synthesis inhibitor, cycloheximde, inhibited the Endoglin expression stimulated by T3, indicating the regulation maybe indirectly. Promoter activity studies indicated that Endoglin positively regulate by T3 through indirect pathway by unknown transcription factor and/or TR directly binding to the response element. Knockdown of Endoglin expression in J7 cells was established. The Endoglin knock-down cells had high ability migration and invasiveness compared to the control cell. Further, Endoglin expression was reduced in 66%of the human hepatocelluar carcinoma. Taken together, T3/TR may play a tumor suppressor.