The Mechanism by Which Agonist and Antagonist Occupied Progesterone Receptors Regulate Target Genes
Annual rept. 15 May 97-14 May 98
BAYLOR COLL OF MEDICINE HOUSTON TX
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Progesterone has been shown to play a role in the proliferation of breast cancer cells, thus the development and use of anti-progestins, such as RU 486, may serve as a useful treatment by blocking the stimulatory effects of progesterone. Progesterone exerts its biological effects through its receptor hPR which belongs to a superfamily of transcription factors. All steroid receptors have been shown to be phosphoproteins and agents which regulate phosphorylation have been demonstrated to affect progesterone receptor action. It is therefore important to study the mechanism by which phosphorylation impinges on progesterone receptor function, and in particular, how it enables 8-Br-cAMP to switch the antagonist RU 486 into an agonist. In this study thus far, three hPR-B specific phosphorylation sites have been mutated to non-phosphorylatable residues an the activities and protein levels of these mutant PR examined.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research