The normal development, lactation related changes, and spontaneous tumors in the mouse mammary gland are well characterized. First, the biology of the mouse mammary gland has been studied for many years. These successes of mouse models of breast cancer stem from the important foundations in mouse mammary biology. Literally thousands of specifically engineered mice have been created to study the pathology, molecular biology, natural history, and response to therapy in breast cancer ( Borowsky 2007). Choosing among the mouse models of breast cancer is not a trivial exercise. Mouse models, particularly the genetically defined models offer a step in the direction of biologic reality. Even xenografting of human cell lines in mice is artificial, short-circuiting the precancer stage, the development of a permissive environment, and eliminating the immune system. Growth in 3D culture is more contextual, but still simplified ( Kenny et al. These cell lines are adapted to growth on two-dimensional (2D) plastic dishes and represent an oversimplified biology out of context. Cell culture lines are the most practical, and a panel of 51 standard cell lines is currently available reflecting most of the intrinsic subtypes of breast cancer ( Neve et al. Experimental models are needed to reflect each part of the array. Breast cancer in women constitutes an array of different diseases, and it is not realistic to consider breast cancer as a single disease. There is no perfect model system for studying breast cancer. The challenge is matching the model to the experimental question. Overall, the many mouse models available are a rich resource for experimental biology with phenocopies of breast cancer subtypes, and a variety of practical advantages. Mammary gland transplantation technology adds a practical and validated method for assessing biologic behavior of selected mammary tissues. Improved genetic engineering, using inducible gene expression, somatic gene transduction, conditional alleles, and crossbreeding for combined/compound genetic engineering yields precise molecular models with exquisite experimental control and phenotypes with comparative pathologic validity. Gene-targeted (knockout) mice, in which tumor suppressors are deleted, develop mammary neoplasms with phenotypes primarily including patterns seen in spontaneous mouse mammary tumors, albeit at higher rates. Transgenic mice, employing strong mammary epithelial promoters to drive oncogenes, develop carcinomas with phenotypes corresponding to the molecular pathway activated. Genetically engineered mice are critical experimental models for the study of breast cancer biology.
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March 2023
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