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

Michael R. Milam, Joseph Celestino, Weiguo Wu, Russell R. Broaddus, Kathleen M. Schmeler, Brian M. Slomovitz, Pamela T. Soliman, David M. Gershenson, Hong Wang, Lora H. Ellenson, Karen H. Lu

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34 Scopus citations

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. 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.

Original languageEnglish (US)
Pages (from-to)247.e1-247.e5
JournalAmerican journal of obstetrics and gynecology
Volume196
Issue number3
DOIs
StatePublished - Mar 2007

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Keywords

  • Pten
  • RAD001
  • endometrial hyperplasia
  • mTOR
  • murine

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Milam, M. R., Celestino, J., Wu, W., Broaddus, R. R., Schmeler, K. M., Slomovitz, B. M., Soliman, P. T., Gershenson, D. M., Wang, H., Ellenson, L. H., & Lu, K. H. (2007). Reduced progression of endometrial hyperplasia with oral mTOR inhibition in the Pten heterozygote murine model. American journal of obstetrics and gynecology, 196(3), 247.e1-247.e5. https://doi.org/10.1016/j.ajog.2006.10.872