|
Pregnancy simulating short term course of hormones protects mice against her2+BRST CA
?A PREVENTIVE TREATMENT IN THE FUTURE?:
Breast Cancer Res. 2007 Jan 26;9(1):R12 [Epub ahead of print]
Hormone-induced protection of mammary tumorigenesis in genetically engineered mouse models.
Rajkumar L,
Kittrell FS,
Guzman RC,
Brown PH,
Nandi S,
Medina D.
ABSTRACT: INTRODUCTION: The experiments reported herein address the question whether a short term hormone treatment can prevent mammary tumorigenesis in two different genetically engineered mouse models. METHODS: Two mouse models, the p53 null mammary epithelial transplant and the c-neu mouse, were exposed to estrogen (E) and progesterone (P) for 2 and 3 weeks, respectively and followed for development of mammary tumors. RESULTS: In the p53 null mammary transplant model, a two week exposure to E and P during the immediate post pubertal stage (2-4 weeks after transplantation) of mammary development decreased mammary tumorigenesis by 70-88%. At 45 weeks after transplantation, analysis of whole mounts of the mammary outgrowths demonstrated the presence of premalignant hyperplasias in both control and hormone treated glands indicating that the hormone treatment strongly affects the rate of premalignant progression. One possible mechanism for the decrease in mammary tumorigenesis may be an altered proliferation activity as the BrdU labeling index was decreased by 85% in the mammary glands of hormone-treated mice. The same short-term exposure administered to mature mice at a time of premalignant development also decreased mammary tumorigenesis by 60%. A role for stroma and/or systemic mediated changes induced by the short term hormone (E/P) treatment was demonstrated by an experiment in which the p53 null mammary epithelial cells were transplanted into the cleared mammary fat pads of previously treated mice. In such mice, the tumor producing capabilities of the mammary cells was also decreased by 60% compared to the same cells transplanted into unexposed mice. In the second set of experiments using the activated Her-2/neu transgenic mouse model, short-term estradiol or estradiol plus progesterone treatment decreased mammary tumor incidence by 67% and 63% and the tumor multiplicity by 91% and 88%, respectively. The growth rate of the tumors arising in the hormone-treated activated Her-2/neu mice was significantly slower than tumors arising in non-hormone treated mice. CONCLUSIONS: As these experiments were performed in model systems that mimic many essential elements of human breast cancer, the results strengthen the rationale for translating this prevention strategy to humans at high risk for developing breast cancer.
PMID: 17257424 [PubMed - as supplied by publisher]
|
Linear Mode
