p53 function is required for hormone-mediated protection of mouse mammary tumorigenesis

Limited hormonal stimulation of the mammary gland during a critical window in postpubertal development imparts a long-lasting protective effect against breast cancer in humans and in rodent models. The hormonal stimulation can be achieved by full-term pregnancy or low doses of estradiol-17beta and progesterone administered for 21 days. The mechanism(s) behind this effect of hormones is not understood at the molecular level. The experiments reported here demonstrate that the absence of p53 tumor suppressor gene function abrogates the protective effect of hormones against carcinogen-induced mammary carcinogenesis in BALB/c mice. This is the first identification of a specific gene product that mediates the protective effect of hormones. Additionally, the experiments highlight the usefulness of transgenic mouse models in the testing of hypotheses derived from the classic rat mammary models.