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.
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