Abstract
The PI3K/PTEN/AKT pathway is the most frequently mutated pathway in endometrial carcinoma. Mouse models are invaluable tools to understand, at the molecular level, the contributions of components of this pathway towards initiation and progression of endometrial carcinoma. This chapter summarizes results of germline and tissue specific knockout mouse models generated to understand how mutations in components of this pathway lead to development of carcinoma and its interactions with other frequently altered pathways like mismatch repair and estrogen signaling. The mouse models show that loss of both alleles of Pten is necessary and sufficient for complex atypical hyperplasia (CAH) to develop but insufficient for progression to carcinoma. Additional events like mutations in Pik3ca or mismatch repair deficiency are required for progression to carcinoma. The models show that the interaction between Pten and estrogen signaling is complex. In the absence of estrogen, Pten loss is sufficient for development of CAH. Additionally, lack of ERĪ± on a background of Pten loss leads to the development of carcinoma.
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Joshi, A., Ellenson, L.H. (2017). PI3K/PTEN/AKT Genetic Mouse Models of Endometrial Carcinoma. In: Hedrick Ellenson, L. (eds) Molecular Genetics of Endometrial Carcinoma. Advances in Experimental Medicine and Biology, vol 943. Springer, Cham. https://doi.org/10.1007/978-3-319-43139-0_9
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DOI: https://doi.org/10.1007/978-3-319-43139-0_9
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