Development of Spontaneous Mammary Tumors in BALB/c-p53+-Mice: Detection of Early Genetic Alterations and the Mapping of BALB/c Susceptibility Genes

摘要

The TP53 tumor suppressor gene is defective in the majority of sporadic breast cancers, and breast cancer is the most frequent tumor type in women with Li-Fraumeni syndrome who inherit germline mutations in TP53. This suggests that p53 is fundamental to the growth regulation and prevention of tumor formation in mammary epithelial cells. Our laboratory has backcrossed the p53-null allele in mice onto the BALB/c genetic background. We have recently described the occurrence of mammary tumors in 55% of female BALB/c-p53+/- mice with a latency of 8-14 months(1). This is in contrast to C57BL/6- and 129/Sv- p53+/- mice, which rarely develop mammary tumors (2), suggesting that the BALB/ c-p53+/- mice serve as a unique model for Li-Fraumeni syndrome (LFS). The experiments proposed in this fellowship are designed to characterize the BALB/c- p53+/- mouse model of breast cancer with respect to the progression of the glands towards tumor formation, and with respect to genetic contributions towards tumor susceptibility which are particular to this strain of mouse.