Polymorphism and Differential Expression of Phase Ⅱ and Phase Ⅲ Detoxification Proteins in Hepatoma Tissues

• Main Authors: Ya-fen Shiau, 蕭雅芬
• Other Authors: Der-an Tsao
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/55040690810982756448

碩士 === 輔英科技大學 === 醫事技術系碩士班 === 95 === Hepatocellular carcinoma (HCC) is a life-threatening and viral-hepatitis-associated disease. It ranks as the first and the second leading causes of death for male and female, respectively, cancer patients in Taiwan. Detoxification proteins eliminate toxic (endogenous and exogenous) substances through oxidation (phaseⅠ), conjugation (phaseⅡ), and transportation (phaseⅢ). UDP-glucuronosyltransferase (UGT), showing glucuronidation activity, plays a major role in the phaseⅡdrug metabolism, while the organic anion transporter, OATP2, is involved in the hepatocellular uptake of a variety of endogenous and xenobiotic substances and drugs. This study was based on the hypothesis that the expressions of detoxification proteins differ among HCC tissues. In order to determine whether genetic variation at UGT1A1 and OATP2 is associated with liver cancer, PCR-RFLP and cloning sequencing experiments were performed to identify genetic variations in UGT1A1 promoter region and nucleotide 211 site in HCC tissues. Five UGT1A1 variations in TA repeat (n = 4–8) in the A(TA)nTAA motifs in the UGT1A1 promoter were found. Polymorphism was also found in the nucleotide 211 site. Furthermore, RT-PCR experiments revealed significantly lower expression of UGT1A1 in HCC than normal liver tissues. To assess the relationship between OATP2 express and liver cancer, RT-PCR experiments were first performed to clone full-length OATP2. Through sequencing analysis, splicing sites in OATP2 RNA were identified. In conclusion, current findings suggest that genetic polymorphism and differential expression are important factors associated with the regulation of detoxification proteins in the HCC tissues.