CYTOSOLIC SULFOTRANSFERASES

描述（改编自摘要）：硫酸化是一种主要的生化反应， 人体内药物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 人细胞溶质硫转移酶（ST），并了解的作用， 药物、外源性物质和内源性底物代谢中的硫酸化 在正常和癌变的人体组织中。 几个人类ST已经被 鉴定 为了实现上述目标，两个 人胞质ST的其它独特形式正在被表征。 的 该项目的具体目标扩大到包括调查 所有人类胞质ST的蛋白质化学和分子生物学。 该建议的重点是六个人胞质ST的表征 还将侧重于科技人员在以下方面的作用： 调节正常和癌性乳腺细胞的雌激素反应性。 该提案的具体目标是：1）表征结构 和最近发现的两种人类ST形式的特性; 2） 研究人类胎盘组织的结构、性质和功能， DHEA-ST和EST的表达; 3）研究STs在正常人乳腺组织中的表达 和癌性乳腺组织，在原发性乳腺上皮细胞中， 乳腺癌细胞系; 4）研究MCF-7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 和用于补充雌激素的雌激素; 5）研究 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.