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Evidence for cancer-associated expression of NADPH oxidase 1 (Nox1)-based oxidase system in the human stomach.
- Source :
-
Free radical biology & medicine [Free Radic Biol Med] 2007 Dec 15; Vol. 43 (12), pp. 1627-38. Date of Electronic Publication: 2007 Sep 14. - Publication Year :
- 2007
-
Abstract
- Helicobacter pylori infection has been suggested to stimulate expression of the NADPH oxidase 1 (Nox1)-based oxidase system in guinea pig gastric epithelium, whereas Nox1 mRNA expression has not yet been documented in the human stomach. PCR of human stomach cDNA libraries showed that Nox1 and Nox organizer 1 (NOXO1) messages were absent from normal stomachs, while they were specifically coexpressed in intestinal- and diffuse-type adenocarcinomas including signet-ring cell carcinoma. Immunohistochemistry showed that Nox1 and NOXO1 proteins were absent from chronic atrophic gastritis (15 cases), adenomas (4 cases), or surrounding tissues of adenocarcinomas (45 cases). In contrast, Nox1 and its partner proteins were expressed in intestinal-type adenocarcinomas (19/21 cases), diffuse-type adenocarcinomas (15/15 cases), and signet-ring cell carcinomas (9/9 cases). Confocal microscopy revealed that Nox1, NOXO1, Nox activator 1, and p22(phox) were predominantly associated with Golgi apparatus in these cancer cells, while diffuse-type adenocarcinomas also contained cancer cells having Nox1 and its partner proteins in their nuclei. Nox1-expressing cancer cells exhibited both gastric and intestinal phenotypes, as assessed by expression of mucin core polypeptides. Thus, the Nox1-base oxidase may be a potential marker of neoplastic transformation and play an important role in oxygen radical- and inflammation-dependent carcinogenesis in the human stomach.
- Subjects :
- Adaptor Proteins, Signal Transducing
Adaptor Proteins, Vesicular Transport genetics
Adaptor Proteins, Vesicular Transport metabolism
Adenocarcinoma enzymology
Adenocarcinoma genetics
Adenoma enzymology
Adenoma genetics
Animals
Carcinoma, Signet Ring Cell enzymology
Carcinoma, Signet Ring Cell genetics
Free Radicals metabolism
Gastric Mucosa enzymology
Gastritis, Atrophic enzymology
Gastritis, Atrophic genetics
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Guinea Pigs
Helicobacter Infections complications
Helicobacter pylori pathogenicity
Humans
Immunohistochemistry
NADPH Oxidase 1
RNA, Messenger genetics
RNA, Messenger metabolism
RNA, Neoplasm genetics
RNA, Neoplasm metabolism
Stomach Neoplasms etiology
Stomach Neoplasms pathology
NADPH Oxidases genetics
NADPH Oxidases metabolism
Stomach Neoplasms enzymology
Stomach Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0891-5849
- Volume :
- 43
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Free radical biology & medicine
- Publication Type :
- Academic Journal
- Accession number :
- 18037128
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2007.08.029