Mouse models of PIK3CA mutations: one mutation initiates heterogeneous mammary tumors.

The phosphoinositide 3-kinase (PI3K) signaling pathway is crucial for cell growth, proliferation, metabolism, and survival, and is frequently deregulated in human cancer, including ~ 70% of breast tumors. PIK3CA, the gene encoding the catalytic subunit p110α of PI3K, is mutated in ~ 30% of breast cancers. However, the exact mechanism of PIK3CA-evoked breast tumorigenesis has not yet been defined. Genetically engineered mouse models are valuable for examining the initiation, development and progression of cancer. Transgenic mice harboring hotspot mutations in p110α have helped to elucidate breast cancer pathogenesis and increase our knowledge about molecular and cellular alterations in vivo. They are also useful for the development of therapeutic strategies. Here, we describe current mouse models of mutant PIK3CA in the mammary gland, and discuss differences in tumor latency and pathogenesis.