Evidence for cancer-associated expression of NADPH oxidase 1 (Nox1)-based oxidase system in the human stomach |
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| Institution: | 1. Division of Interventional Therapy, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China;2. Division of Oncology, Jining First People''s Hospital, Jining, Shandong 272011, China;3. Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China;4. Division of Pediatric Surgery, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China;5. Shandong Sino-US Cooperation Research Center for Translational Medicine, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China;1. Clinical Laboratory Division, Shimane University Hospital, 89-1, Enya, Izumo, Shimane 693-8501, Japan;2. Blood Transfusion Division, Shimane University Hospital, 89-1, Enya, Izumo, Shimane 693-8501, Japan;3. Department of Pediatrics, Faculty of Medicine, Shimane University, 89-1, Enya, Izumo, Shimane 693-8501, Japan |
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| 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 p22phox 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. |
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