title: Reduced progression of endometrial hyperplasia with oral mTOR inhibition in the Pten heterozygote murine model.
abstract: OBJECTIVE
  Phosphatase and tensin homolog (PTEN) mutations are associated with human endometrial cancers, and PTEN heterozygote(+/-) mice have a high rate of endometrial neoplasia. The objective of this study was to evaluate an oral mTOR inhibitor (mTOR-I) on the reduction of endometrial hyperplasia in an animal model.
  
  
  METHODS
  Three groups of 10 female mice were treated from age 20-26 weeks: group A, Pten wild type with mTOR-I; group B, Pten+/- with placebo; and group C, Pten +/- with mTOR-I. Rates of hyperplasia and markers of proliferation and apoptosis were evaluated.
  
  
  RESULTS
  Higher grade hyperplasia occurred in a significantly greater percentage of the untreated Pten+/- group B (80%; 8/10) compared with groups A (0%; 0/10) and C (20%; 2/10; P < .02). The treated Pten+/- mTOR-I group C also demonstrated significantly increased apoptosis (P < .002) and decreased proliferation index (P < .02) compared with the untreated group B.
  
  
  CONCLUSIONS
  Oral mTOR inhibition decreases the progression of endometrial hyperplasia in the Pten heterozygote murine model through decreased cell proliferation and increased apoptosis.
authors.affiliation: Department of Gynecologic Oncology, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Milam
authors.forename: Joseph
authors.initials: J
authors.lastname: Celestino
authors.forename: Weiguo
authors.initials: W
authors.lastname: Wu
authors.forename: Russell R
authors.initials: RR
authors.lastname: Broaddus
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Schmeler
authors.forename: Brian M
authors.initials: BM
authors.lastname: Slomovitz
authors.forename: Pamela T
authors.initials: PT
authors.lastname: Soliman
authors.forename: David M
authors.initials: DM
authors.lastname: Gershenson
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Lora H
authors.initials: LH
authors.lastname: Ellenson
authors.forename: Karen H
authors.initials: KH
authors.lastname: Lu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018450:Disease Progression; D004714:Endometrial Hyperplasia / Q000188:drug therapy* / Q000235:genetics*; D000068338:Everolimus; D005260:Female; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011494:Protein Kinases / Q000187:drug effects*; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D058570:TOR Serine-Threonine Kinases
chemical_list: D000068338:Everolimus; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D020123:Sirolimus