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Dysregulated expression of NADPH oxidase 1 (Nox1) in gastric cancer
Author(s) -
Rokutan Kazuhito,
Tominaga Kumiko,
Kuwano Yuki,
Masuda Kiyoshi,
Sekiyama Atsuo,
TeshimaKondo Shigetada
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1262-b
The Helicobacter pylori ‐associated carcinogenic pathway of intestinal‐type gastric carcinomas involves well‐characterized sequential stages: superficial gastritis, atrophic gastritis, intestinal metaplasia, and carcinomas. An intestine‐specific CDX2 is one of the most likely candidates linked with the induction of intestinal metaplasia. NADPH oxidase 1 (Nox1) is implicated in the pathogenesis of oxygen radical‐dependent carcinogenesis. Northern hybridization and RT‐PCR showed that the Nox1 mRNA was absent in the normal stomach, while it was specifically expressed in intestinal‐ and diffuse‐type adenocarcinomas. Nox1 protein was expressed in intestinal (15/17 cases), diffuse‐type carcinomas (7/7), and signet‐ring cell carcinomas (10/10 cases), while it was absent in accompanying normal or chronic atrophic tissues with metaplasia. We confirmed that GATA6 and CDX2 were essential for the basal promoter activity of the human Nox1 gene. In fact, Nox1‐possessing cancer cells expressed GATA6 and CDX1/2. Furthermore, we found that a Th1 cytokine IFN‐γ activated transcription of the Nox1 gene. STAT1 and GAS motif located at −3960 to −3645 bp mediated the IFN‐γ‐stimulated transcription. These results suggest that intestine‐specific transcription factors plus Th1 cytokines may cause dysregulated expression of Nox1, which may participate in inflammation‐dependent carcinogenesis in the stomach.