Cadherin-6 type 2, K-cadherin (CDH6) is regulated by mutant p53 in the fallopian tube but is not expressed in the ovarian surface

摘要: // Subbulakshmi Karthikeyan 1 , Daniel D. Lantvit Dam Hee Chae Joanna E. Burdette Center for Biomolecular Sciences, Department of Medicinal Chemistry and Pharmacognosy, College Pharmacy, University Illinois at Chicago, IL 60607, USA Correspondence to: Burdette, email: joannab@uic.edu Keywords: high-grade serous ovarian carcinoma, p53 mutation, fallopian tube, tissue specific mutant transgenic mouse model, cadherins Received: March 24, 2016     Accepted: August 09, Published: 22, 2016 ABSTRACT High-grade cancer (HGSOC) is the most lethal gynecological malignancy may arise in either tube epithelium (FTE) or surface (OSE). A mutation reported 96% HGSOC, frequently R273 R248. The goal this study was to identify gene targets FTE that are altered by p53, but not OSE. Gene analysis revealed both R248 reduces CDH6 expression oviduct, detected murine OSE cells. R273H induced SLUG FOXM1 while R248W did induce only modestly increased FOXM1, which correlated with less migration as compared . An oviduct PAX8 Cre/+ /p53 R270H/+ model created confirmed vivo repressed sufficient stabilize alone. Overexpression null OVCAR5 cells decreased levels indicating a gain-of-function. knockdown oviductal restored repression ChIP direct binding on promoter. NSC59984, small molecule degrades rescued expression. In summary, expressed ovary, p53. further validations aide establishing markers inform upon cell origin high grade tumors.