the role of lef1 in endometrial gland formation and carcinogenesislef1在子宫内膜腺形成的作用和致癌作用.pdfVIP

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the role of lef1 in endometrial gland formation and carcinogenesislef1在子宫内膜腺形成的作用和致癌作用.pdf

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the role of lef1 in endometrial gland formation and carcinogenesislef1在子宫内膜腺形成的作用和致癌作用

The Role of LEF1 in Endometrial Gland Formation and Carcinogenesis 1. 1. 1 1 1 1 Dawne N. Shelton , Hubert Fornalik , Traci Neff , Soo Yeun Park , David Bender , Koen DeGeest , 2 2 3 2 1 Xiaoming Liu , Weiliang Xie , David K. Meyerholz , John F. Engelhardt , Michael J. Goodheart * 1 Department of Obstetrics and Gynecology, Holden Comprehensive Cancer Center, The University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States of America, 2 Department of Anatomy and Cell Biology, The University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America, 3 Department of Pathology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States of America Abstract Endometrial carcinoma is the most common gynecologic cancer, yet the mechanisms underlying this disease process are poorly understood. We hypothesized that Lef1 is required for endometrial gland formation within the uterus and is overexpressed in endometrial cancer. Using Lef1 knockout (KO) mice, we compared uterine gland development to wild-type (WT) controls, with respect to both morphology and expression of the Lef1 targets, cyclin D1 and MMP7. We characterized the dynamics of Lef1 protein expression during gland development and the mouse estrus cycle, by immunostaining and Western blot. Finally, we investigated the roles of cyclin D1 and MMP7 in gland and cancer formation in the mouse, and assessed the relevance of Lef1 to human cancer by comparing expression levels in cancerous and normal endometrial tissues. Lef1 upregu