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


Journal

NPJ breast cancer
ISSN: 2374-4677
Titre abrégé: NPJ Breast Cancer
Pays: United States
ID NLM: 101674891

Informations de publication

Date de publication:
24 Nov 2020
Historique:
received: 12 11 2019
accepted: 21 10 2020
entrez: 10 12 2020
pubmed: 11 12 2020
medline: 11 12 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33298921
doi: 10.1038/s41523-020-00204-6
pii: 10.1038/s41523-020-00204-6
pmc: PMC7686348
doi:

Types de publication

Journal Article

Langues

eng

Pagination

62

Subventions

Organisme : NCI NIH HHS
ID : R01 CA169175
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA186107
Pays : United States
Organisme : Division of Cancer Prevention, National Cancer Institute (NCI Division of Cancer Prevention)
ID : T32CA009001
Organisme : Division of Cancer Prevention, National Cancer Institute (NCI Division of Cancer Prevention)
ID : R01CA160246

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Auteurs

Sonali Jindal (S)

Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 2720 SW Moody Ave., Mailing Code: KR-CDCB, Portland, OR, 97201, USA.
Knight Cancer Institute, Oregon Health & Science University, 2720 SW Moody Ave., Mailing Code: KR-ADM, Portland, OR, 97201, USA.

Nathan D Pennock (ND)

Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 2720 SW Moody Ave., Mailing Code: KR-CDCB, Portland, OR, 97201, USA.

Alex Klug (A)

Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 2720 SW Moody Ave., Mailing Code: KR-CDCB, Portland, OR, 97201, USA.

Jayasri Narasimhan (J)

Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 2720 SW Moody Ave., Mailing Code: KR-CDCB, Portland, OR, 97201, USA.

Andrea Calhoun (A)

Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 2720 SW Moody Ave., Mailing Code: KR-CDCB, Portland, OR, 97201, USA.

Michelle R Roberts (MR)

Department of Dermatology, Massachusetts General Hospital, 50 Staniford Street, Suite 200, Boston, MA, 02114, USA.

Rulla M Tamimi (RM)

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02114, USA.

A Heather Eliassen (AH)

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02114, USA.

Sheila Weinmann (S)

Center for Health Research, Kaiser Permanente Northwest, 3800 N. Interstate Ave., Portland, OR, 97227, USA.

Virginia F Borges (VF)

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.
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.

Pepper Schedin (P)

Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, 2720 SW Moody Ave., Mailing Code: KR-CDCB, Portland, OR, 97201, USA. schedin@ohsu.edu.
Knight Cancer Institute, Oregon Health & Science University, 2720 SW Moody Ave., Mailing Code: KR-ADM, Portland, OR, 97201, USA. schedin@ohsu.edu.
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. schedin@ohsu.edu.
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. schedin@ohsu.edu.

Classifications MeSH