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S-nitrosylated and non-nitrosylated COX2 have differential expression and distinct subcellular localization in normal and breast cancer tissue

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 cl...

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Autores principales: Jindal, Sonali, Pennock, Nathan D., Klug, Alex, Narasimhan, Jayasri, Calhoun, Andrea, Roberts, Michelle R., Tamimi, Rulla M., Eliassen, A. Heather, Weinmann, Sheila, Borges, Virginia F., Schedin, Pepper
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686348/
https://www.ncbi.nlm.nih.gov/pubmed/33298921
http://dx.doi.org/10.1038/s41523-020-00204-6
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author Jindal, Sonali
Pennock, Nathan D.
Klug, Alex
Narasimhan, Jayasri
Calhoun, Andrea
Roberts, Michelle R.
Tamimi, Rulla M.
Eliassen, A. Heather
Weinmann, Sheila
Borges, Virginia F.
Schedin, Pepper
author_facet Jindal, Sonali
Pennock, Nathan D.
Klug, Alex
Narasimhan, Jayasri
Calhoun, Andrea
Roberts, Michelle R.
Tamimi, Rulla M.
Eliassen, A. Heather
Weinmann, Sheila
Borges, Virginia F.
Schedin, Pepper
author_sort Jindal, Sonali
collection PubMed
description 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.
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spelling pubmed-76863482020-12-03 S-nitrosylated and non-nitrosylated COX2 have differential expression and distinct subcellular localization in normal and breast cancer tissue Jindal, Sonali Pennock, Nathan D. Klug, Alex Narasimhan, Jayasri Calhoun, Andrea Roberts, Michelle R. Tamimi, Rulla M. Eliassen, A. Heather Weinmann, Sheila Borges, Virginia F. Schedin, Pepper NPJ Breast Cancer Article 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. Nature Publishing Group UK 2020-11-24 /pmc/articles/PMC7686348/ /pubmed/33298921 http://dx.doi.org/10.1038/s41523-020-00204-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Jindal, Sonali
Pennock, Nathan D.
Klug, Alex
Narasimhan, Jayasri
Calhoun, Andrea
Roberts, Michelle R.
Tamimi, Rulla M.
Eliassen, A. Heather
Weinmann, Sheila
Borges, Virginia F.
Schedin, Pepper
S-nitrosylated and non-nitrosylated COX2 have differential expression and distinct subcellular localization in normal and breast cancer tissue
title S-nitrosylated and non-nitrosylated COX2 have differential expression and distinct subcellular localization in normal and breast cancer tissue
title_full S-nitrosylated and non-nitrosylated COX2 have differential expression and distinct subcellular localization in normal and breast cancer tissue
title_fullStr S-nitrosylated and non-nitrosylated COX2 have differential expression and distinct subcellular localization in normal and breast cancer tissue
title_full_unstemmed S-nitrosylated and non-nitrosylated COX2 have differential expression and distinct subcellular localization in normal and breast cancer tissue
title_short S-nitrosylated and non-nitrosylated COX2 have differential expression and distinct subcellular localization in normal and breast cancer tissue
title_sort s-nitrosylated and non-nitrosylated cox2 have differential expression and distinct subcellular localization in normal and breast cancer tissue
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686348/
https://www.ncbi.nlm.nih.gov/pubmed/33298921
http://dx.doi.org/10.1038/s41523-020-00204-6
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