NADPH oxidase 1 is highly expressed in human large and small bowel cancers

Autor: Mariam M. Konaté, Krishnendu Roy, Hala R. Makhlouf, Jiamo Lu, Jennifer L. Meitzler, Han Liu, Yongzhong Wu, Donna Butcher, Smitha Antony, Guojian Jiang, Rodrigo F. Chuaqui, James H. Doroshow, Agnes Juhasz
Rok vydání: 2019
Předmět:
0301 basic medicine
Colorectal cancer
Biochemistry
0302 clinical medicine
Superoxides
Adenocarcinomas
Intestine
Small
Medicine and Health Sciences
Small interfering RNAs
Staining
Multidisciplinary
Tissue microarray
biology
Cell Staining
Oxides
Neoplasm Proteins
Gene Expression Regulation
Neoplastic
Nucleic acids
Chemistry
Oncology
030220 oncology & carcinogenesis
NOX1
Colonic Neoplasms
Physical Sciences
cardiovascular system
NADPH Oxidase 1
Immunohistochemistry
Adenocarcinoma
Medicine
Antibody
Anatomy
HT29 Cells
Research Article
medicine.drug_class
Colon
Science
Monoclonal antibody
Research and Analysis Methods
Models
Biological
Carcinomas
Gene Expression Regulation
Enzymologic
03 medical and health sciences
medicine
Genetics
Humans
Molecular Biology Techniques
Non-coding RNA
Molecular Biology
Immunohistochemistry Techniques
Colorectal Cancer
Chemical Compounds
Cancers and Neoplasms
Biology and Life Sciences
medicine.disease
Gene regulation
Gastrointestinal Tract
Histochemistry and Cytochemistry Techniques
030104 developmental biology
Specimen Preparation and Treatment
Cancer cell
biology.protein
Cancer research
Immunologic Techniques
RNA
Gene expression
Caco-2 Cells
Digestive System
Cloning
Zdroj: PLoS ONE
PLoS ONE, Vol 15, Iss 5, p e0233208 (2020)
ISSN: 1932-6203
Popis: To facilitate functional investigation of the role of NADPH oxidase 1 (NOX1) and associated reactive oxygen species in cancer cell signaling, we report herein the development and characterization of a novel mouse monoclonal antibody that specifically recognizes the C-terminal region of the NOX1 protein. The antibody was validated in stable NOX1 overexpression and knockout systems, and demonstrates wide applicability for Western blot analysis, confocal microscopy, flow cytometry, and immunohistochemistry. We employed our NOX1 antibody to characterize NOX1 expression in a panel of 30 human colorectal cancer cell lines, and correlated protein expression with NOX1 mRNA expression and superoxide production in a subset of these cells. Although a significant correlation between oncogenic RAS status and NOX1 mRNA levels could not be demonstrated in colon cancer cell lines, RAS mutational status did correlate with NOX1 expression in human colon cancer surgical specimens. Immunohistochemical analysis of a comprehensive set of tissue microarrays comprising over 1,200 formalin-fixed, paraffin-embedded tissue cores from human epithelial tumors and inflammatory disease confirmed that NOX1 is overexpressed in human colon and small intestinal adenocarcinomas, as well as adenomatous polyps, compared to adjacent, uninvolved intestinal mucosae. In contradistinction to prior studies, we did not find evidence of NOX1 overexpression at the protein level in tumors versus histologically normal tissues in prostate, lung, ovarian, or breast carcinomas. This study constitutes the most comprehensive histopathological characterization of NOX1 to date in cellular models of colon cancer and in normal and malignant human tissues using a thoroughly evaluated monoclonal antibody. It also further establishes NOX1 as a clinically relevant therapeutic target in colorectal and small intestinal cancer.
Databáze: OpenAIRE
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