Evidence for cancer-associated expression of NADPH oxidase 1 (Nox1)-based oxidase system in the human stomach.
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.
Department of Stress Science, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Kumiko
K
Tominaga
Tsukasa
T
Kawahara
Toshiaki
T
Sano
Kazunori
K
Toida
Yuki
Y
Kuwano
Hideyuki
H
Sasaki
Tomoko
T
Kawai
Shigetada
S
Teshima-Kondo
Kazuhito
K
Rokutan
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics; D000236:Adenoma / Q000201:enzymology / Q000235:genetics; D000818:Animals; D018279:Carcinoma, Signet Ring Cell / Q000201:enzymology / Q000235:genetics; D005609:Free Radicals / Q000378:metabolism; D005753:Gastric Mucosa / Q000201:enzymology; D005757:Gastritis, Atrophic / Q000201:enzymology / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006168:Guinea Pigs; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D007150:Immunohistochemistry; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000235:genetics* / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D005609:Free Radicals; C476419:NOXO1 protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human