Transgenic mouse models of human breast cancer

The pathogenesis of human breast cancer is thought to involve multiple gene tic events, the majority of which fall into two categories, gain of functio n mutations in protooncogenes such as c-myc, cyclin D1, ErbB-2 and various growth factors which are involved in supporting cell growth, division and s urvival, and loss of function mutations in so called 'tumor suppressor' gen es, such as p53, which are involved in preventing unrestrained cellular gro wth. A number of mouse systems exist to address the significance of these m utations in the pathogenesis of breast cancer including transgenic mice exp ressing high levels of a specific gene in target tissues and knockout mice in which specific genes have been ablated via homologous recombination. Mor e recently, the:combination of these techniques to create bigenics as well as the use of 'knockin' and conditional tissue specific gene targeting stra tegies have allowed the models more reflective of the human disease to be d evised. Studies with these models have not only implicated particular genet ic events in the progression of the disease but have emphasized the complex , multi-step nature of breast cancer progression. These models also provide the opportunity to study various aspects of the pathogenesis of this disea se, from hormonal effects to responses to chemotherapeutic drugs. It is hop ed that through the combined use of these models, and the further developme nt of more relevant models, that a deeper understanding of this disease and the generation of new therapeutic agents will result.