title: Cell-specific conditional deletion of Pten in the uterus results in differential phenotypes.
abstract: OBJECTIVE
  Endometrial cancer (EMC) is the most common gynecological malignancy. The etiology and the cell types that are conducive to EMC are not completely understood, provoking further studies. Our objective was to determine whether deletion of Pten specifically in the uterine stroma and myometrium induces cancer or manifests different phenotypes.
  
  
  METHODS
  Pten(Amhr2(d/d)) mice with conditional deletion of Pten in the mouse uterine stroma and myometrium, but not in the epithelium, were generated by mating floxed Pten mice and anti-Mullerian hormone type 2 receptor (Amhr2)-Cre mice. The phenotypes were compared between Pten(f/f) and Pten(Amhr2(d/d)) uteri.
  
  
  RESULTS
  We show that conditional deletion of Pten in the mouse uterine stroma and myometrium, but not in the epithelium, fails to generate EMC even at the age of 5 months. Surprisingly Pten deletion by Amhr2-Cre transformed a large number of myometrial cells into adipocytes with lipid accumulation, possibly a result of increased levels of SREBP1 and PPARγ which regulate adipose differentiation.
  
  
  CONCLUSIONS
  These results provide evidence that deletion of Pten specifically in the stroma and myometrium does not result in EMC in female mice examined up to 5 months of age but alters the myocytes to adipocytes and mimics histologic similarities with lipoleiomyomas in humans, raising the possibility of using this mouse model to further explore the cause of the disease.
authors.affiliation: Division of Reproductive Sciences, The Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA. takiko.daikoku@cchmc.org
authors.forename: Takiko
authors.initials: T
authors.lastname: Daikoku
authors.forename: Lindsey
authors.initials: L
authors.lastname: Jackson
authors.forename: Valérie
authors.initials: V
authors.lastname: Besnard
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Whitsett
authors.forename: Lora Hedrick
authors.initials: LH
authors.lastname: Ellenson
authors.forename: Sudhansu K
authors.initials: SK
authors.lastname: Dey
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D002454:Cell Differentiation; D016889:Endometrial Neoplasms / Q000209:etiology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D047495:PPAR gamma / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000502:physiology*; D010641:Phenotype; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D014599:Uterus / Q000473:pathology*
chemical_list: D047495:PPAR gamma; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse