Abstract

The continuing goal of this project is to develop methods to evaluate environmental mammary carcinogens, and to define factors and mechanisms related to susceptibility to mammary cancer. In this renewal we will continue to develop and evaluate both direct and mediated rat mammary cell mutagenesis sytems. These mutagenesis systems, together with the quantitation of B(a)P- and DMBA-DNA adduct formation and removal as well as metabolism, will be used to: 1) compare the interaction of DMBA and B(a)P with mammary cells in vivo and in vitro; and 2) delineate the relationship of these parameters and susceptibility to induced breast cancer in two rat models. The rat models include one in which Sprague-Dawley rats, which are highly susceptible to PAH-induced mammary cancer, will be compared to Long Evans rats, which are less susceptible. The second rat model will compare virgin Sprague-Dawley rats (susceptible to PAH-induced mammary carcinogenesis) to mid-pregnant Sprague-Dawley rats (relatively resistant). This project may produce model systems and information that may ultimately lead to the lowering of the morbidity and mortality of breast cancer, the major lethal cancer of women.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA028954-05
Application #
3168453
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1981-01-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715

  Publications

Smits, Bart M G; Haag, Jill D; Rissman, Anna I et al. (2013) The gene desert mammary carcinoma susceptibility locus Mcs1a regulates Nr2f1 modifying mammary epithelial cell differentiation and proliferation. PLoS Genet 9:e1003549
Leng, Ning; Dawson, John A; Thomson, James A et al. (2013) EBSeq: an empirical Bayes hierarchical model for inference in RNA-seq experiments. Bioinformatics 29:1035-43
Gould, Michael N (2009) The utility of comparative genetics to inform breast cancer prevention strategies. Genetics 183:409-12
Nelson, Stephanie E; Gould, Michael N; Hampton, John M et al. (2005) A case-control study of the HER2 Ile655Val polymorphism in relation to risk of invasive breast cancer. Breast Cancer Res 7:R357-64
Zan, Yunhong; Haag, Jill D; Chen, Kai-Shun et al. (2003) Production of knockout rats using ENU mutagenesis and a yeast-based screening assay. Nat Biotechnol 21:645-51
Haag, Jill D; Shepel, Laurie A; Kolman, Bradley D et al. (2003) Congenic rats reveal three independent Copenhagen alleles within the Mcs1 quantitative trait locus that confer resistance to mammary cancer. Cancer Res 63:5808-12
Kendziorski, C M; Newton, M A; Lan, H et al. (2003) On parametric empirical Bayes methods for comparing multiple groups using replicated gene expression profiles. Stat Med 22:3899-914
Watson, Philip A; Kim, Kwanghee; Chen, Kai-Shun et al. (2002) Androgen-dependent mammary carcinogenesis in rats transgenic for the Neu proto-oncogene. Cancer Cell 2:67-79
Shepel, L A; Gould, M N (1999) The genetic components of susceptibility to breast cancer in the rat. Prog Exp Tumor Res 35:158-69
Shepel, L A; Lan, H; Brasic, G M et al. (1998) Mapping of 55 new rat microsatellite markers from chromosome-specific libraries. Mamm Genome 9:622-8

Showing the most recent 10 out of 37 publications