CYTOSOLIC SULFOTRANSFERASES

描述(摘自摘要)：硫酸盐化是一种主要的生化反应 药物在人体内的生物转化和排泄途径 内源性化合物，如类固醇和儿茶酚胺。总目标 这个项目的目的是研究细菌的生物化学和分子生物学。 人类胞浆硫转移酶(STS)的表达及了解其作用 药物、外源物质和内源底物代谢中的硫酸盐化 在正常和癌变的人体组织中。已经有几个人类性传播疾病 已确认身份。继续前一个应用程序的目标，两个 人类胞浆性ST的其他独特形式正在被表征。这个 该项目的具体目标被扩大到包括对 所有人类胞浆STS的蛋白质化学和分子生物学。 这项建议的重点是六个人类胞浆STS的特征 它们已经确定，并将重点放在STS在 调节正常和癌变乳腺细胞的雌激素反应。 这项建议的具体目的是：1)确定结构的特征 以及最近发现的两种人类ST；2) 研究人类PSTs的结构、性质和功能， DHEA-ST和EST：3)检测正常人STS的表达 和癌变的乳腺组织，在原代乳腺上皮细胞中，以及在 乳腺癌细胞株；4)研究MCF-7乳腺癌细胞对乳腺癌细胞的反应性 表达EST或过表达P-PST至17-雌二醇的癌细胞 以及用于补充雌激素的雌激素；5)研究其作用 EST和P-PST在乳腺癌细胞对内源性、 治疗和环境雌激素。

DESCRIPTION (Adapted from Abstract): Sulfation is a major biochemical pathway in humans for the biotransformation and excretion of drugs and endogenous compounds, such as steroids and catecholamines. The overall goal of this project is to investigate the biochemistry and molecular biology of the human cytosolic sulfotransferases (STs) and to understand the role of sulfation in the metabolism of drugs, xenobiotics and endogenous substrates in normal and cancerous human tissues. Several human STs have already been identified. Continuing with the aims of the previous application, two additional unique forms of human cytosolic ST are being characterized. The Specific Aims of this project are expanded to include the investigation of the protein chemistry and molecular biology of all human cytosolic STs. This proposal focuses on the characterization of the six human cytosolic STs which have been identified and will also focus on the role of the STs in regulating estrogen-responsiveness of normal and cancerous breast cells. The Specific Aims of this proposal are to: 1) characterize the structure and properties of the two recently identified forms of human ST; 2) investigate the structure, properties and functions of the human PSTs, DHEA-ST and EST; 3) investigate the expression of the human STs in normal and cancerous breast tissue, in primary breast epithelial cells, and in breast cancer cell lines; 4) investigate the responsiveness of MCF-7 breast cancer cells either expressing EST or over-expressing P-PST to 17-estradiol and to estrogens used for estrogen supplementation; 5) investigate the role of EST and P-PST in the response of breast cancer cells to endogenous, therapeutic and environmental estrogens.