Mammary Tumor Heterogeneity in wt-ErbB-2 Transgenic Mice
Abstract:Phenotypic and biological heterogeneity was studied in a single transgenic mouse model to determine the level of biological variance. We analyzed 1,258 tumors from 417 MMTV-wt-ErbB-2 transgenic mice, subdivided by casein or soy-based dietary randomization and hormonal treatment. Variance in tumor histologic features, growth pattern, invasion, metastases, and multi-focality were detected in untreated and treated mice. Ninety-three percent (1,174/1,258) of tumors had the solid growth pattern widely reported in this model. However, among the solid tumors, a spectrum of growth patterns, from well-circumscribed tumors with a pseudocapsule to locally invasive or highly aggressive, metastatic subtype, was observed. Of the non-solid tumors, glandular features were prominent in 84 (7%). Adenocarcinomas included papillary, acinar/glandular, and adenosquamous subtypes. Adenosquamous tumors were exclusively observed in the group of mice treated on a short-term basis with estrogen. In contrast to the reported literature for this transgenic mouse model, mammary tumors were multifocal in the majority of cases (303 of 417 mice, or 73%).
Results of this extensive study of a single transgenic model of mammary tumorigenesis indicate phenotypic and biological heterogeneity not previously associated with this transgenic mouse. These data support a complex, multistep process of carcinogenesis and clonal evolution, with biological and phenotypic variance similar to that observed in human mammary cancer development.
Document Type: Research Article
Affiliations: 1: Department of Pathology and College of Medicine, Oklahoma University Health Sciences Center (OUHSC), Oklahoma City, Oklahoma 2: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California 3: Department of Pathology and College of Medicine, Oklahoma University Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, Department of Pathology, College of Medicine, Korea University, Seoul, Korea 4: Department of Pathology and College of Medicine, Oklahoma University Health Sciences Center (OUHSC), Oklahoma City, Oklahoma, Department of Pathology, BMSB 451, 940 Stanton L. Young Blvd, Oklahoma City, Oklahoma 73104
Publication date: June 1, 2004
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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