Studying of regulation mechanism and physiological significance of PTTG1 and Furin by thyroid hormone

• Main Authors: Ruey-Nan Chen, 陳瑞楠
• Other Authors: K. H. Lin
• Format: Others
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/5h89q2

博士 === 長庚大學 === 基礎醫學研究所 === 96 === Thyroid hormone is a pleiotropic regulator of growth, differentiation and tissue homeostasis in higher organisms that acts through the control of target gene expression. Major T3 actions are mediated by specific high affinity nuclear receptors which are encoded by two genes, TRα and TRβ. Many studies reported on the relationship between circulating thyroid hormone levels, thyroid disease and human cancer. In 1986, a connection between TR and cancer became evident when the chicken TRα1 was characterized as the c-erbA proto-oncogene, the cellular counterpart of the retroviral v-erbA oncogene. v-erbA causes erythroleukemias and sarcomas in birds, and hepatocellular carcinomas in transgenic mice. Recently, many studies have analyzed the presence of quantitative or qualitative alterations in the expression of TR genes in different type of human neoplasias. While their role in liver tumor generation or progression is currently unclear. This study characterized pituitary tumor transforming gene 1 (PTTG1) and furin previously identified in cDNA microarray screening for T3-responsive genes in HepG2-TRα1 cells. We elucidated the molecular mechanism of PTTG1 and furin regulation by T3 in isogenic HepG2 cell lines. The experimental results also revealed that T3-induced gene expression in human HCC cell lines resembles that observed in animal model studies. Furthermore, the clinicopathological significance of PTTG1 and furin expression in HCC were also investigated. The experimental results indicated that PTTG1 gene expression is mediated by Sp1 and is indirectly downregulated by T3. Additionally, T3 directly regulates furin gene expression, thereby enhancing its invasiveness. Nevertheless, the detailed role of TR during carcinogenesis requires further study.