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Cancerogenesis in Helicobacter pylori infected stomach – role of growth factors, apoptosis and cyclooxygenases

Piotr C. Konturek, Stanisław J. Konturek, Piotr Pierzchalski, Władysław Bielański, Aleksandra Duda, Krzysztof Marlicz, Teresa Starzyńska, Eckhart G. Hahn

Med Sci Monit 2001; 7(5): RA1092-1107 :: ID: 509379

Abstract

Background: Epidemiological and animal studies demonstrated a link between gastric cancer (GC) or mucosal associated lymphoid tissue (MALT) lymphoma and chronic infection with Helicobacter pylori (H. pylori). The exact mechanism responsible for the development of GC and MALT-lymphoma in H. pylori-infected patients still remains obscure. This report is designed to overview the molecular biology, especially the gene expression and histochemical manifestation of gastrin and other growth factors such as transforming growth factor alpha (TGFa) and hepatocyte growth factor (HGF) in the GC before and after eradication of H. pylori. Furthermore, gene expression of cyclooxygenase-1 (COX-1) and COX-2 and apoptosis-related proteins such as Bax and Bcl-2 are discussed.
Material/Methods: The findings originate from two series of patients; Series I involving 337 GC patients and 400 age- and gender-matched controls and series 2 including 20 MALT-lymphoma patients and 40 matched controls.
Results: An overall H.pylori-seropositivity reached about 80% in GC and about 90% in MALT-lymphoma, significantly higher than in non-cancer controls (60%). The prevalence of CagA-positive strains was about twice as high (about 70%) in GC and MALT-lymphomas as in sex- and age-matched controls. Expression of gastrin was detected in antrum of all tested patients but also in majority (90%) of GCs and MALT-lymphomas tumor tissue. HGF and TGFa were expressed more frequently in GC tissue than in normal fundic mucosa. COX-1 was similarly expressed in GC and MALT as in intact mucosa, while COX-2 mRNA was detected only in tumor tissue, being attenuated by H.pylori eradication in GC and abolished by this therapy in MALT-lymphoma. The plasma levels of a-amidated gastrin in GC and MALT were several folds higher than in controls. Gene expression of bcl-2 was detected in all, while bax - only in about 50% of GC samples.
Conclusions: Infection with H. pylori, especially that expressing CagA-positivity, is primum movens in developing GC and MALT-lymphoma and the upregulation of growth factors, particularly of gastrin, and COX-2 and dysregulation of the Bax/Bcl-2 system seem to contribute to gastric cancerogenesis.

Keywords: Helicobacter pylori, gastrin, growth factors

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750