Exercise and p53 gene dosage effects on gene expression profiles in mammary glands of MMTV-Wnt-1 transgenic mice.

A173 Previously, we have seen that calorie restriction (CR) can delay mammary tumorigenesis in p53 heterozygous (p53 +/- ) MMTV-Wnt-1 (Wnt-1) transgenic mice, while treadmill exercise of a moderate intensity hastens tumorigenesis in these same mice. We hypothesized that exercise may be detrimental due to the p53 deficiency, and therefore sought to determine the global changes in mammary gland gene expression in p53 +/+ and p53 +/- mice with and without exercise. We further examined whether there was an interaction between exercise and p53 genotype. Thirteen-week-old female p53 +/+ :Wnt-1 and p53 +/- : Wnt-1 transgenic mice were singly housed and randomly assigned to either moderate exercise treadmill training or non-exercise control groups. At the end of the six-week treatment period gene expression profiles of mammary tissue from 3-5 tumor-free mice/group were compared using Affymetrix 430 2.0 GeneChips and analyzed using R, Bioconductor, and Ingenuity Pathway analysis software. There was a significant interaction between p53 status and exercise for 775 genes (p