Accession Number : ADA332010

Title :   Regulation of Agonist - and Antagonist - Mediated Activation of Human Progesterone Receptors by Phosphorylation.

Descriptive Note : Final rept. 1 Jul 94-30 Jun 97,

Corporate Author : BAYLOR COLL OF MEDICINE HOUSTON TX

Personal Author(s) : Zhang, Yixian

PDF Url : ADA332010

Report Date : JUL 1997

Pagination or Media Count : 30

Abstract : Phosphoprotein progesterone receptor (PR) is a key mediator of sex hormone progesterone, which regulates the development and differentiation of many organs including mammary glands. Aberrant activity of PR may be involved in breast cancer development. We have been interested in the effect of phosphorylation on PR activity and antagonist activity of RU 486 to agonist activity switch. We sought to first identify phosphorylation sites in human PR in T47D breast cancer cells so that the significance of phosphorylation of individual site can be studied using site-directed mutagenesis approach. Nine phosphorylation sites were previously identified. Our current studies revealed a new site and one more site remains to be identified. The effect of several signal transduction pathways on the RU 486 antagonist activity to agonist activity switch has been tested. RU 486 became a stronger antagonist in the presence of epidermal growth factor and ras oncogene, suggesting that multiple pathways can contribute to the agonist activity of RU 486. I have also compared the activity of wild type hPR with mutants Ala4OO and Glu4OO. The transcriptional activity of Ala400 was much lower than that of the wild type, while Glu400's activity was comparable to wild type. The mutagenesis studies suggest that phosphorylation is important for the activity of hPR.

Descriptors :   *PHOSPHORYLATION, *BREAST CANCER, RECEPTOR SITES(PHYSIOLOGY), MAMMARY GLANDS, PROGESTERONE.

Subject Categories : Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE