Accession Number : ADA333275

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

Descriptive Note : Annual rept 1 Sep 96-31 Aug 97

Corporate Author : M D ANDERSON CANCER CENTER HOUSTON TX

Personal Author(s) : Hursting, Stephen D.

PDF Url : ADA333275

Report Date : SEP 1997

Pagination or Media Count : 17

Abstract : 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-hydroxyphenyl)restriction 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.1/p21 (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-phenyl)retinamide 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.

Descriptors :   *PROTEINS, *BREAST CANCER, HORMONES, NEOPLASMS, GENES, MICE, CARCINOGENS, CELLS(BIOLOGY), PREVENTION, CHEMOTHERAPY, MAMMARY GLANDS, SUPPRESSORS.

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE