**7.1 Genetically engineered mouse models**

Genetic models have also clearly established AIB1 as an oncogene in multiple cancer types. Genetically engineered mouse models that overexpress AIB1 have been shown to increase incidence and growth of tumors, as well as significantly increase hyperplasia in the breast [7]. This is not solely due to its interaction with the estrogen receptor, the same mice presented an increase in tumors in hormone independent tissues, such as lung, skin, and bone, suggesting the oncogenic role of AIB1 may be mediated by a variety of different tissue specific transcription factor interactions [46, 81]. Removal of the NCOA3 gene that encodes AIB1 in v-Ha-Ras driven mouse model of breast cancer also delayed tumor formation by negatively impacting growth factor signaling [50]. In breast cancer studies, it is clear that AIB1 exerts its oncogenic potential through hormone receptor signaling and by positively affecting many pro-proliferative pathways.

There have also been genetic models implicating AIB1 as a critical mediator of the development and maintenance of hormone responsive and castration resistant prostate cancer. In hormone sensitive prostate cancer, AIB1 mediates its effects through androgen receptor activity, eventual castration resistant/hormone insensitive disease was marked by AIB1 potentiation of Akt-mTOR signaling (similar to studies in the breast) [81–83]. Taken together, these data suggest that AIB1 is critical for the formation and progression of many cancer types, in both hormone dependent and independent settings. Especially in the hormone-independent diseases, it is critical to study the binding partners of AIB1 in order to better understand how AIB1 is acting as an oncogene.
