title: Development and characterization of a novel rat model of estrogen-induced mammary cancer.
abstract: The ACI rat model of 17β-estradiol (E2)-induced mammary cancer is highly relevant for use in establishing the endocrine, genetic, and environmental bases of breast cancer etiology and identifying novel agents and strategies for preventing breast cancer. E2 treatment rapidly induces mammary cancer in female ACI rats and simultaneously induces pituitary lactotroph hyperplasia and adenoma. The pituitary tumors can result in undesired morbidity, which compromises long-term studies focused on mammary cancer etiology and prevention. We have defined the genetic bases of susceptibility to E2-induced mammary cancers and pituitary tumors and have utilized the knowledge gained in these studies to develop a novel inbred rat strain, designated ACWi, that retains the high degree of susceptibility to E2-induced mammary cancer exhibited by ACI rats, but lacks the treatment-related morbidity associated with pituitary lactotroph hyperplasia/adenoma. When treated with E2, female ACWi rats developed palpable mammary cancer at a median latency of 116 days, an incidence of 100% by 161 days and exhibited an average of 15.6 mammary tumors per rat following 196 days of treatment. These parameters did not differ from those observed for contemporaneously treated ACI rats. None of the E2-treated ACWi rats were killed before the intended experimental end point due to any treatment-related morbidity other than mammary cancer burden, whereas 20% of contemporaneously treated ACI rats exhibited treatment-related morbidity that necessitated premature killing. The ACWi rat strain is well suited for use by those in the research community, focusing on breast cancer etiology and prevention.
authors: McArdle Laboratory for Cancer ResearchDepartment of Oncology, School of Medicine and Public HealthSchool of Medicine and Public HealthMolecular and Environmental Toxicology CenterSchool of Medicine and Public HealthUniversity of Wisconsin Carbone Cancer Center, University of Wisconsin, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
authors: Kirsten L
authors: KL
authors: Dennison
authors: McArdle Laboratory for Cancer ResearchDepartment of Oncology, School of Medicine and Public HealthSchool of Medicine and Public HealthMolecular and Environmental Toxicology CenterSchool of Medicine and Public HealthUniversity of Wisconsin Carbone Cancer Center, University of Wisconsin, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
authors: Nyssa Becker
authors: NB
authors: Samanas
authors: McArdle Laboratory for Cancer ResearchDepartment of Oncology, School of Medicine and Public HealthSchool of Medicine and Public HealthMolecular and Environmental Toxicology CenterSchool of Medicine and Public HealthUniversity of Wisconsin Carbone Cancer Center, University of Wisconsin, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
authors: Quincy Eckert
authors: QE
authors: Harenda
authors: McArdle Laboratory for Cancer ResearchDepartment of Oncology, School of Medicine and Public HealthSchool of Medicine and Public HealthMolecular and Environmental Toxicology CenterSchool of Medicine and Public HealthUniversity of Wisconsin Carbone Cancer Center, University of Wisconsin, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
authors: Maureen Peters
authors: MP
authors: Hickman
authors: McArdle Laboratory for Cancer ResearchDepartment of Oncology, School of Medicine and Public HealthSchool of Medicine and Public HealthMolecular and Environmental Toxicology CenterSchool of Medicine and Public HealthUniversity of Wisconsin Carbone Cancer Center, University of Wisconsin, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
authors: Nicole L
authors: NL
authors: Seiler
authors: McArdle Laboratory for Cancer ResearchDepartment of Oncology, School of Medicine and Public HealthSchool of Medicine and Public HealthMolecular and Environmental Toxicology CenterSchool of Medicine and Public HealthUniversity of Wisconsin Carbone Cancer Center, University of Wisconsin, 1111 Highland Avenue, Madison, Wisconsin 53705, USA McArdle Laboratory for Cancer ResearchDepartment of Oncology, School of Medicine and Public HealthSchool of Medicine and Public HealthMolecular and Environmental Toxicology CenterSchool of Medicine and Public HealthUniversity of Wisconsin Carbone Cancer Center, University of Wisconsin, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
authors: Lina
authors: L
authors: Ding
authors: McArdle Laboratory for Cancer ResearchDepartment of Oncology, School of Medicine and Public HealthSchool of Medicine and Public HealthMolecular and Environmental Toxicology CenterSchool of Medicine and Public HealthUniversity of Wisconsin Carbone Cancer Center, University of Wisconsin, 1111 Highland Avenue, Madison, Wisconsin 53705, USA McArdle Laboratory for Cancer ResearchDepartment of Oncology, School of Medicine and Public HealthSchool of Medicine and Public HealthMolecular and Environmental Toxicology CenterSchool of Medicine and Public HealthUniversity of Wisconsin Carbone Cancer Center, University of Wisconsin, 1111 Highland Avenue, Madison, Wisconsin 53705, USA McArdle Laboratory for Cancer ResearchDepartment of Oncology, School of Medicine and Public HealthSchool of Medicine and Public HealthMolecular and Environmental Toxicology CenterSchool of Medicine and Public HealthUniversity of Wisconsin Carbone Cancer Center, University of Wisconsin, 1111 Highland Avenue, Madison, Wisconsin 53705, USA shull@oncology.wisc.edu.
authors: James D
authors: JD
authors: Shull
mesh_terms: D000818:Animals; D004958:Estradiol; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D010641:Phenotype; D010902:Pituitary Gland / Q000473:pathology; D011919:Rats, Inbred Strains
chemical_list: D004958:Estradiol
keywords: ACI rat; ACWi rat; Copenhagen rat; breast cancer; estradiol