title: PI3K/PTEN/AKT Genetic Mouse Models of Endometrial Carcinoma.
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 ERα on a background of Pten loss leads to the development of carcinoma.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA. Ayj2002@med.cornell.edu.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Joshi
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.
authors.forename: Lora Hedrick
authors.initials: LH
authors.lastname: Ellenson
mesh_terms: D000818:Animals; D058534:Class I Phosphatidylinositol 3-Kinases; D004195:Disease Models, Animal; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C546639:Pik3ca protein, mouse; C487757:Pten protein, mouse
keywords: ERalpha; Mlh1; Mouse models; Pik3ca; Pten