Author:
Sato Sho,Gillette Michael,de Santiago Pamela R.,Kuhn Eric,Burgess Michael,Doucette Kristen,Feng Yi,Mendez-Dorantes Carlos,Ippoliti Paul J.,Hobday Sara,Mitchell Marilyn A.,Doberstein Kai,Gysler Stefan M.,Hirsch Michelle S.,Schwartz Lauren,Birrer Michael J.,Skates Steven J.,Burns Kathleen H.,Carr Steven A.,Drapkin Ronny
Abstract
AbstractLong interspersed element 1 (LINE-1) open reading frame 1 protein (ORF1p) expression is a common feature of many cancer types, including high-grade serous ovarian carcinoma (HGSOC). Here, we report that ORF1p is not only expressed but also released by ovarian cancer and primary tumor cells. Immuno-multiple reaction monitoring-mass spectrometry assays showed that released ORF1p is confidently detectable in conditioned media, ascites, and patients’ plasma, implicating ORF1p as a potential biomarker. Interestingly, ORF1p expression is detectable in fallopian tube (FT) epithelial precursors of HGSOC but not in benign FT, suggesting that ORF1p expression in an early event in HGSOC development. Finally, treatment of FT cells with DNA methyltransferase inhibitors led to robust expression and release of ORF1p, validating the regulatory role of DNA methylation in LINE-1 repression in non-tumorigenic tissue.
Funder
Claneil Foundation
National Institutes of Health
Helene Ross Bogutz Fund for Ovarian Cancer Early Detection
Mike and Patti Hennessy Foundation
Ovarian Cancer Research Alliance
China Scholarship Council
Honorable Tina Brozman Foundation
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
Shooting for a Cure
Deutsche Forschungsgemeinschaft
Rivkin Center for Ovarian Cancer
Marjorie S. Stanek and Lowell H. Dubrow Ovarian Cancer Research Center Endowed Fund
Maggie’s Memorial Fund
Publisher
Springer Science and Business Media LLC
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