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.
OBJECTIVE: Phosphatase and tensin homolog (PTEN) mutations are associated with humanendometrial 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.
Authors: Adrienne S McCampbell; Heather A Harris; Judy S Crabtree; Richard C Winneker; Cheryl L Walker; Russell R Broaddus Journal: Cancer Prev Res (Phila) Date: 2010-02-23
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Authors: Brian M Slomovitz; Karen H Lu; Taren Johnston; Robert L Coleman; Mark Munsell; Russell R Broaddus; Cheryl Walker; Lois M Ramondetta; Thomas W Burke; David M Gershenson; Judith Wolf Journal: Cancer Date: 2010-08-02 Impact factor: 6.860
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