The Physiological Role of Progesterone Receptors in Breast Development and Tumorigenesis.
Annual rept. 1 Sep 96-31 Aug 97,
BAYLOR COLL OF MEDICINE HOUSTON TX
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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 in determining the 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 vitm. This suggests that these receptors are likely to have different physiological roles in breast development and tumorigenesis. To date no in vivo model exists to address this question. The objectives of this proposal are to establish the collective and individual physiological roles of these receptors in breast development and carcinogenesis in vivo. To achieve the above objective, nouse lines will be examined in which the PR status is altered by either a null mutation or selective ablation of the A or B forms of the PR. The physiological analysis of these mutant mouse lines will provide valuable information on the selective contribution of the PRA and PRB to breast development and tumorigenesis in vivo. This information will improve prognostic capabilities with regard to analysis of PR status in breast tumors as well as improved treatment strategies.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research