The Mechanism of How PRSS22 is Positively Regulated by Thyroid Hormone

• Main Authors: You Ching Wang, 王柚晴
• Other Authors: K. H. Lin
• Format: Others
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/97065307979096001943

碩士 === 長庚大學 === 生物醫學研究所 === 98 === Thyroid hormone (3, 5, 3’-triiodo-L-thyronine, T3) play a central role in growth, metabolic homeostasis, development and differentiation. Thyroid hormone action is mediated by the nuclear thyroid hormone receptors (TRs). In previous study, SILAC (Stable isotope labeling with amino acids in cell culture) was performed to identify proteins regulated by T3. There were many genes regulated by T3 including PRSS22. PRSS22 is a member of the human serine proteases family. Previous studies show that serine proteases were involved in the posttranslational processing of many polypeptides and played important roles in the regulation of physiological processes, including coagulation, fibrinolysis, development, malignancy, and inflammation. However, the underlying mechanism and the physiological role of T3 in the regulation of PRSS22 in hepatocellular carginogenesis were not clear. In this study, we demonstrated that mRNA and protein expression levels were up-regulated after T3 treatment in TR-overexpressed hepatoma cell lines. To localize the regulatory region in PRSS22, serial deletions of the promoter and ChIP assay were performed. The evidences showed that the TRE on the PRSS22 promoter was localized between the -628/-350 region. Additionally, to explore the effects of PRSS22 on cellular function, we demonstrated that ectopic expression of PRSS22 promotes cell migration and invasion in Huh7 hepatoma cells. Together, these experimental findings suggest that PRSS22, which is positively regulated by T3, plays an important role in cell migration and invasion.