Characterization of Wnt-1 Transgenic Mice (with and without p53-deficiency) as Models of Spontaneous Mammary Tumorigenesis for Chemoprevention Studies

摘要

Wnt-1 transgenic(TG) mice develop mammary tumors at a high rate by 1 year of age due to mammary gland overexpression of the Wnt-1 oncogene. - We have shown that p53-deficiency accelerates mammary tumorigenesis in these mice, with 100% of p53-1- Wnt-1 TG mice and p53+/-Wnt-1 TG mice dead from mammary tumors by 5 months and 9 months of age, respectively. To test their response to cancer preventive regimens, we randomized 104 female p53+/- Wnt-1 TG mice (5 weeks of age, 20 mice/treatment) to receive: (1) control diet (AIN-76A diet); (2) fenretinide (AIN 76A diet with 0.04% w/w fenretinide); (3) fluasterone (AIN- 76A diet with 0.2% fluasterone); (4) soy (AIN-76A diet with 0.45% phytochemical- enriched soy extract); or (5) a calorie restriction regimen (40% reduction in carbohydrate calorie intake relative to the control group). All mice were euthanized once a tumor reached 1.5 cm in diameter. We found that, relative to the control group (MTD=15.7 weeks), the fenretinide (MTD=23.1 weeks, p=O.Ol) and fluasterone (MTD=23.l weeks, p=O.006) and soy (MTD =21 weeks, p=O.04) groups displayed moderate but significant delays in tumor development and death, while the calorie restricted group (MTD > 40 weeks; p