Accession Number : ADA322066

Title :   The Physiological Role of Progesterone Receptors in Breast Development and Tumorigenesis.

Descriptive Note : Annual rept. 1 Sep 95-31 Aug 96,

Corporate Author : BAYLOR COLL OF MEDICINE HOUSTON TX

Personal Author(s) : Conneely, Orla M.

PDF Url : ADA322066

Report Date : SEP 1996

Pagination or Media Count : 17

Abstract : Progesterone and estrogen are the key steroidal hormones involved in breast development and tumorigenesis. The effects of progesterone and estrogen are mediated through specific intracellular receptors and the status of these receptors in breast tumors has been used as an important prognostic indicator of probability of disease free survival and response to hormonal therapies. The progesterone receptor (PR) is composed of two isoforms, PRA and PRB which have different transactivation functions in vitro and are likely to have different physiological roles in breast development and tumorigenesis. To date no in vivo model exists to address this question. To generate such a model, we have proposed to selectively ablate expression of PRA or B in mice by gene targeting. We have devised two alternative strategies to introduce subtle mutations into the mouse PR gene by gene targeting in embryonic stem (ES)cells. To date, we have produced three out of four gene targeting constructs needed for homologous recombination using these strategies. Further, we have successfully completed the first of two targeted integration steps in ES cells using one strategy. Finally, using the PR null mutant mice we previously generated, we provide evidence that the cell cycle protein Dl cyclin may be a key mediator of the mammary developmental responses that are specific to progesterone.

Descriptors :   *PHYSIOLOGICAL EFFECTS, *RECEPTOR SITES(PHYSIOLOGY), *PROGESTERONE, *BREAST CANCER, HORMONES, PROTEINS, NEOPLASMS, MUTATIONS, IN VITRO ANALYSIS, GENES, MICE, IN VIVO ANALYSIS, EMBRYOS, MAMMARY GLANDS, STEROIDS, ESTROGENS.

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE