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

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.