Reduced progression of endometrial hyperplasia with oral mTOR inhibition in the Pten heterozygote murine model

Am J Obstet Gynecol. 2007 Mar;196(3):247.e1-5. doi: 10.1016/j.ajog.2006.10.872.


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.

Study design: 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.

Conclusion: Oral mTOR inhibition decreases the progression of endometrial hyperplasia in the Pten heterozygote murine model through decreased cell proliferation and increased apoptosis.

MeSH terms

  • Administration, Oral
  • Animals
  • Disease Progression
  • Endometrial Hyperplasia / drug therapy*
  • Endometrial Hyperplasia / genetics*
  • Everolimus
  • Female
  • Heterozygote
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • PTEN Phosphohydrolase / genetics*
  • Protein Kinases / drug effects*
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives*
  • TOR Serine-Threonine Kinases


  • Everolimus
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • PTEN Phosphohydrolase
  • Pten protein, mouse
  • Sirolimus