Hepsin is up-regulated by thyroid hormone and inhibits cell proliferation

• Main Authors: Yu Tung Lin, 林羽佟
• Other Authors: K. H. Lin
• Format: Others
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/25642335768973223907

碩士 === 長庚大學 === 生物醫學研究所 === 100 === Thyroid hormone (T3) and its receptor (TR) control differentiation, growth and metabolism. To study the regulation mechanism of T3 in TRα-overexpressed hepatoma cell line (HepG2-TRα) , oligonucleotide microarray analysis was performed. Some genes were regulated by T3/TR, including Hepsin (HPN) . Recently, many studies indicate that Hepsin is involved in tumor progression, and used as a prostate cancer biomarker. In TR-overexpressed hepatoma cell line, Hepsin mRNA and protein expression level are both up-regulated after T3 treatment. The cycloheximide treatment reveal that Hepsin was direct regulated by T3/TR. Utilizing promoter assay and ChIP assay to determine the TR binding site of Hepsin promoter was located within +506/+523. Furthermore, Hepsin is down-regulated in hepatocellular carcinoma (HCC) tissue. To study the physiological function of Hepsin in HCC cell lines, Hepsin knockdown cells were established in Mahlavu. Cyclin E and CDK2 expression level were up-regulated in Hepsin knockdown cells, then accelerated cell cycle G1 to S phase transition, result in increase cell proliferation. In conclusion, the result indicate the up-regulation Hepsin following T3/TR treatment may contribute cell proliferation, and demonstrate the tumor suppressor role of Hepsin in tumorigenesis.