1. Expression of COX-2, mPGE synthase 1, MDR-1 (P-GP) and BCL-XL: a molecular pathway of H pylori related-gastric carcinogenesis
- Author
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Gaetano Salvatore, Alfredo Budillon, Gaetano De Rosa, Fabiana Tatangelo, Gerardo Nardone, Paola Patrignani, Maria Di Benedetto, Maria G. Sciulli, Alba Rocco, Dino Vaira, Stefania Staibano, Federico Perna, NARDONE G, ROCCO A, VAIRA D., STAIBANO S, BUDILLON A, TATANGELO F, SCIALLI MG, PERNA F, SALVATORE G, DI BENEDETTO M, DE ROSA G, PATRIGNANI P, Nardone, GERARDO ANTONIO PIO, Rocco, Alba, Vaira, D, Staibano, Stefania, Budillon, A, Tatangelo, F, Sciulli, Mg, Perna, F, Salvatore, Gaetano, Di Benedetto, M, DE ROSA, Gaetano, and Patrignani, P.
- Subjects
Adult ,Male ,medicine.medical_specialty ,bcl-X Protein ,medicine.disease_cause ,Helicobacter Infections ,Pathology and Forensic Medicine ,Helicobacter pylory ,Stomach Neoplasms ,Gene expression ,gastric carcinogenesi ,medicine ,Gastric mucosa ,Humans ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,MDR-1 ,Aged ,Prostaglandin-E Synthases ,Chi-Square Distribution ,Helicobacter pylori ,biology ,Stomach ,Membrane Proteins ,Cancer ,Bcl xL ,Anatomical pathology ,Middle Aged ,medicine.disease ,biology.organism_classification ,Immunohistochemistry ,Enzyme Activation ,Intramolecular Oxidoreductases ,Isoenzymes ,mPGE-Synthase ,medicine.anatomical_structure ,Proto-Oncogene Proteins c-bcl-2 ,cyclooxygenase-2 ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,Gastritis ,Immunology ,Cancer research ,Female ,Carcinogenesis - Abstract
Helicobacter pylori up-regulates cyclo-oxygenase-2 (COX-2) expression, which in turn is involved in tumourigenesis. Recently, a causal link between COX-2 and multidrug resistance 1 (MDR-1) gene expression, implicated in cancer chemoresistance, has been demonstrated. Thus, the expression of COX-2 and the downstream enzyme involved in PGE2 biosynthesis, microsomal PGE-synthase1 (mPGES1), was correlated with P-gp, the product of MDR-1, and the anti-apoptotic protein, Bcl-xL, in gastric biopsies from patients with H pylori infection and in patients with gastric cancer. In a retrospective analysis of endoscopic and pathology files, 40 H pylori-negative patients (Hp-), 50 H pylori-positive patients who responded to eradication therapy (Hp+R), 84 H pylori-positive patients who did not respond to eradication therapy (Hp+NR), and 30 patients with gastric cancer (18 intestinal and 12 diffuse types) were selected. COX-2, mPGES1, P-gp, and Bcl-xL were detected by immunohistochemistry. COX-2, mPGES1, P-gp, and Bcl-xL expression was undetectable in gastric mucosa from Hp- patients. By contrast, COX-2 and mPGES1 expression was detected in 42% and 44% of Hp+R patients, respectively, and in up to 66% (range 63-66%) of Hp+NR patients (p < 0.05). The expression of COX-2 and mPGES1 correlated significantly (p < 0.0001) with that of P-gp and Bcl-xL. High levels of COX-2, mPGES1, P-gp, and Bcl-xL expression were found in intestinal-type gastric cancer samples. In conclusion, H pylori-dependent induction of COX-2 and mPGES1 is associated with enhanced production of P-gp and Bcl-xL that may contribute to gastric tumourigenesis and resistance to therapy.
- Published
- 2004