Characterization of Wnt-1 Transgenic Mice (with and without p53-deficiency) as Models of Spontaneous Mammary Tumorigenesis for Chemoprevention Studies
Annual rept 1 Sep 96-31 Aug 97
M D ANDERSON CANCER CENTER HOUSTON TX
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The ectopic expression of the Wnt-1 proto-oncogene in Wnt-1 transgenic Wnt-1 TG mice results in mammary gland hyperplasia and early adenocarcinoma development. Mammary tumorigenesis is further accelerated in p53-deficient Wnt-1 TG mice generated by mating Wnt-1 TG mice with p53-knockout mice. The purpose of the proposed study is to evaluate the effects of calorie restriction and the chemopreventive agents dehydroepiandrosterone, genistein and N-4-hydroxyphenylrestriction on spontaneous mammary tumorigenesis in Wnt-1 TG mice with and without p53-deficiency. We are also evaluating the mechanisms underlying interventions that modulate spontaneous mammary tumorigenesis in these mice by measuring the expression of Waf.1p21 a p53-related cell cycle regulator, Bcl-2 a p53-related apoptotic regulator, retinoic acid receptor beta associated with the chemopreventive efficacy of N-4-hydroxy-phenylretinamide and Brca-1 a putative tumor suppressor gene associated with familial breast cancer. This study will provide the initial characterization of Wnt-1 TG mice and p53-deficient Wnt-1 TG mice as models of spontaneous mammary tumorigenesis for cancer prevention studies. We have successfully developed a colony of these mice over the course of the year and have generated mice for the initial aim of the study, which is to assses the effects of our interventions on spontaneous mammary tumor development in these mice.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research