Evidence for cancer-associated expression of NADPH oxidase 1 (Nox1)-based oxidase system in the human stomach.

Tominaga, Kumiko; Kawahara, Tsukasa; Sano, Toshiaki; Toida, Kazunori; Kuwano, Yuki; Sasaki, Hideyuki; Kawai, Tomoko; Teshima-Kondo, Shigetada; Rokutan, Kazuhito

Tominaga, Kumiko; Kawahara, Tsukasa; Sano, Toshiaki; Toida, Kazunori; Kuwano, Yuki; Sasaki, Hideyuki; Kawai, Tomoko; Teshima-Kondo, Shigetada; Rokutan, Kazuhito.

Afiliación

Tominaga K; Department of Stress Science, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.

Free Radic Biol Med ; 43(12): 1627-38, 2007 Dec 15.

Article en En | MEDLINE | ID: mdl-18037128

RESUMEN

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.

Asunto(s)

NADPH Oxidasas/genética; NADPH Oxidasas/metabolismo; Neoplasias Gástricas/enzimología; Neoplasias Gástricas/genética; Proteínas Adaptadoras Transductoras de Señales; Proteínas Adaptadoras del Transporte Vesicular/genética; Proteínas Adaptadoras del Transporte Vesicular/metabolismo; Adenocarcinoma/enzimología; Adenocarcinoma/genética; Adenoma/enzimología; Adenoma/genética; Animales; Carcinoma de Células en Anillo de Sello/enzimología; Carcinoma de Células en Anillo de Sello/genética; Radicales Libres/metabolismo; Mucosa Gástrica/enzimología; Gastritis Atrófica/enzimología; Gastritis Atrófica/genética; Regulación Enzimológica de la Expresión Génica; Regulación Neoplásica de la Expresión Génica; Cobayas; Infecciones por Helicobacter/complicaciones; Helicobacter pylori/patogenicidad; Humanos; Inmunohistoquímica; NADPH Oxidasa 1; ARN Mensajero/genética; ARN Mensajero/metabolismo; ARN Neoplásico/genética; ARN Neoplásico/metabolismo; Neoplasias Gástricas/etiología; Neoplasias Gástricas/patología

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / NADPH Oxidasas Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Free Radic Biol Med Asunto de la revista: BIOQUIMICA / MEDICINA Año: 2007 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos

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