Female athymic nude mice (NCr-nu) were purchased from Taconic Farms (Hudson, NY). All mouse studies were approved by the Institutional Animal Care and Use Committee and the animals were cared for in accordance with guidelines set by the American Association for Accreditation of Laboratory Animal Care and the US Public Health Service Policy on Human Care and Use of Laboratory Animals. For therapeutic experiments, ISHIKAWA uterine cancer cells were directly injected into the uterine horn and to create an orthotopic mouse model of uterine cancer as previously described (20 (link)). Forty mice were randomly allocated into 4 treatment groups: control, onapristone (10 mg/kg subcutaneously, dissolving the drug in castor oil containing 10% benzyl benzoate, daily) (22 (link)), trametinib (1 mg/kg orally, dissolving the drug in 30% PEG400/0.5% Tween80/5% propylene glycol, daily) (23 (link)), or onapristone plus trametinib. Treatment was initiated 2 weeks after cancer cell injection into the uterine horn. After 6 weeks of treatment, the mice were sacrificed, and total body weight, tumor location and weight, and number of tumor nodules were recorded. Tumor specimens were preserved in either optimum cutting temperature medium (Miles Inc., Elkhart, IN) (for frozen slides), or fixed in formalin (for paraffin slides) for further analysis.