@article{edfcc4ce79d648f29ab4570c454fccb8,
title = "S-nitrosylated and non-nitrosylated COX2 have differential expression and distinct subcellular localization in normal and breast cancer tissue",
abstract = "Immunohistochemical (IHC) staining in breast cancer shows both gain and loss of COX2 expression with disease risk and progression. We investigated four common COX2 antibody clones and found high specificity for purified human COX2 for three clones; however, recognition of COX2 in cell lysates was clone dependent. Biochemical characterization revealed two distinct forms of COX2, with SP21 recognizing an S-nitrosylated form, and CX229 and CX294 recognizing non-nitrosylated COX2 antigen. We found S-nitrosylated and non-nitrosylated COX2 occupy different subcellular locations in normal and breast cancer tissue, implicating distinct synthetic/trafficking pathways and function. Dual stains of ~2000 breast cancer cases show early-onset breast cancer had increased expression of both forms of COX2 compared to postmenopausal cases. Our results highlight the strengths of using multiple, highly characterized antibody clones for COX2 IHC studies and raise the prospect that S-nitrosylation of COX2 may play a role in breast cancer biology.",
author = "Sonali Jindal and Pennock, {Nathan D.} and Alex Klug and Jayasri Narasimhan and Andrea Calhoun and Roberts, {Michelle R.} and Tamimi, {Rulla M.} and Eliassen, {A. Heather} and Sheila Weinmann and Borges, {Virginia F.} and Pepper Schedin",
note = "Funding Information: We thank Hadley Holden and Marcelia Brown for immunohistochemistry and technical assistance; Sam Sivagnanam for assistance with hierarchical clustering analyses; Kristin Muessig for assistance with human subject research regulations, Christopher Rivard (University of Colorado, Denver) for COX2 knockout mouse tissue; Santiago Zelenay (CRUK Manchester Institute, Manchester UK) and Caetano Reis e Sousa (The Francis Crick Institute, London, UK) for the mouse melanoma cell line harboring a BRAFV600E mutation (Wt), and the subline deficient for COX1 and COX2; Naoki Oshimori for IF imaging; Lisa Coussens laboratory for insightful discussion on the project; and Weston Anderson for manuscript drafting, editing, and development. We would like to thank the participants and staff of the YWBCTP at University of Colorado Hospital and NHS1 for their valuable contributions, as well as the involved State Cancer Registries. This work was supported by National Center for Advancing Translational Sciences (NCATS), CCTSI UL1 TR001082 for REDCap database support; KCI{\textquoteright}s Cancer Center Support Grant P30CA69533; NIH R01CA169175 to V.F.B. and P.S.; NIH R01CA160246 to A.H.E.; T32CA009001 to M.R.R.; UM1 and P01 CA186107 and CA87969 to M. Stampfer; OCTRI-CHR NW Kaiser Permanente to P.S. and S.J., the Kay Yow Cancer Fund and the Eccles Foundation to P.S., and Grohne Family Foundation to V.F.B. and P.S. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
doi = "10.1038/s41523-020-00204-6",
language = "English (US)",
volume = "6",
journal = "npj Breast Cancer",
issn = "2374-4677",
publisher = "Nature Publishing Group",
number = "1",
}