The p53-Deficient Mouse as a Breast Cancer Model

Abstract : The p53 tumor suppressor gene is mutated in almost half of all human cancers and in roughly 30-40% of breast cancers. In order to better understand the role of p53 mutation and loss in breast cancer progression, we have developed a mouse model which is genetically programmed to develop mammary cancer in the presence and absence of p53. By comparison of the mammary tumorigenesis process between the p53 positive and p53 negative animals we hope to obtain further insights into the mechanisms by which loss of p53 accelerates tumor progression. In the first two years of this grant we have shown that in the absence of p53 mammary tumors arise sooner and grow faster than mammary tumors with intact p53. We have also shown that tumors without p53 have higher levels of chromosomal instability and higher rates of cell proliferation than tumors with p53. Rates of apoptosis (programmed cell death) were shown to be low and not significantly different between p53 positive and negative tumors. Thus, our results appear to validate the model as useful in elucidating the role of p53 loss in the tumorigenesis process and underscore the likelihood that p53 has multiple functions in its prevention of tumor formation and progression.