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NPJ Breast Cancer. 2020 Nov 24;6(1):62. doi: 10.1038/s41523-020-00204-6.

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

NPJ breast cancer

Sonali Jindal, Nathan D Pennock, Alex Klug, Jayasri Narasimhan, Andrea Calhoun, Michelle R Roberts, Rulla M Tamimi, A Heather Eliassen, Sheila Weinmann, Virginia F Borges, Pepper Schedin

Affiliations

  1. Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 2720 SW Moody Ave., Mailing Code: KR-CDCB, Portland, OR, 97201, USA.
  2. Knight Cancer Institute, Oregon Health & Science University, 2720 SW Moody Ave., Mailing Code: KR-ADM, Portland, OR, 97201, USA.
  3. Department of Dermatology, Massachusetts General Hospital, 50 Staniford Street, Suite 200, Boston, MA, 02114, USA.
  4. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
  5. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02114, USA.
  6. Center for Health Research, Kaiser Permanente Northwest, 3800 N. Interstate Ave., Portland, OR, 97227, USA.
  7. School of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, MS8117, RC-1S, 8401K, 12801 E 17th Ave., Aurora, CO, 80045, USA.
  8. Young Women's Breast Cancer Translational Program, School of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, MS8117, RC-1S, 8401K, 12801 E 17th Ave., Aurora, CO, 80045, USA.
  9. Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 2720 SW Moody Ave., Mailing Code: KR-CDCB, Portland, OR, 97201, USA. [email protected].
  10. Knight Cancer Institute, Oregon Health & Science University, 2720 SW Moody Ave., Mailing Code: KR-ADM, Portland, OR, 97201, USA. [email protected].
  11. School of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, MS8117, RC-1S, 8401K, 12801 E 17th Ave., Aurora, CO, 80045, USA. [email protected].
  12. Young Women's Breast Cancer Translational Program, School of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, MS8117, RC-1S, 8401K, 12801 E 17th Ave., Aurora, CO, 80045, USA. [email protected].

PMID: 33298921 PMCID: PMC7686348 DOI: 10.1038/s41523-020-00204-6

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.

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