Physiological Role of Progesterone Receptors in Breast Development and Tumorigenesis

摘要

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 vitro. This suggests that these receptors are likely to have different physiological roles in breast development and tumorigenesis. 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 objective, genetic mouse models have been generated 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 provides 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.