Study of Human TR4 Nuclear Receptor in Insulin-like Growth Factor-I Gene Regulation

• Main Authors: Jhih-Hao Wang, 王志浩
• Other Authors: Han-Jung, Lee
• Format: Others
• Language: en_US
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/876u9p

碩士 === 國立東華大學 === 生物技術研究所 === 96 === Nuclear receptors are a family of transcription factors. They can bind to hormone response elements of target genes, control their expression, and many important physiology processes. The ligands of many nuclear receptors have not been identified, so they are called orphan receptors. TR4 is an orphan receptor. TR4 can control gene expression, animal growth and development, and the function of the liver. Collins and associates observed insulin-like growth factor-I (IGF-I) decreases in the blood and the liver of TR4 gene knockout mice in 2003. IGF-I regulated the body growth of human and mice. Therefore, we hypothesized TR4 was an potential activator of IGF-I gene expression. To demonstrate our hypothesis, we selected four sequence, IGF-DR2，IGF-DR4，IGF-DR6 and IGF-rDR4, to perform electrophoresis mobility assay (EMSA) and dual-luciferase assay. The result of EMSA suggested TR4 could bind to IGF-DR6 and IGF-rDR4. The result of dual-luciferase assay suggested TR4 interacted with IGF-DR6 and GF-rDR4 in HeLa cell line acted a repressor. However, the result was opposite our original hypothesis. The reason was that HeLa cell line wasn’t derived from the liver tissue. Our study showed TR4 might participate to regulate IGF-I gene expression. Furthermore, we will detect the effect of TR4 on IGF-I gene expression to demonstrate whether TR4 can regulate IGF-I gene expression in cells.