Expression of hepatocyte growth factor, transforming growth factor alpha, apoptosis related proteins Bax and Bcl-2, and gastrin in human gastric cancer

Citation
Pc. Konturek et al., Expression of hepatocyte growth factor, transforming growth factor alpha, apoptosis related proteins Bax and Bcl-2, and gastrin in human gastric cancer, ALIM PHARM, 15(7), 2001, pp. 989-999
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology,"da verificare
Journal title
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
ISSN journal
0269-2813 → ACNP
Volume
15
Issue
7
Year of publication
2001
Pages
989 - 999
Database
ISI
SICI code
0269-2813(200107)15:7<989:EOHGFT>2.0.ZU;2-3
Abstract
Background: Gastric cancer is one of the most frequent neoplasms and a lead ing cause of the death world-wide, In recent years, epidemiological and ani mal studies demonstrated a link. between gastric cancer and chronic infecti on with H. pylori. The exact mechanism responsible for the development of g astric cancer in H. pylori-infected patients still remains unclear. There i s evidence that the up-regulation of certain growth factors could play an i mportant role in the promotion of the gastric carcinogenesis. Aims: The present study was designed to determine the gene expression of ma jor known growth factors such as transforming growth factor alpha (TGF alph a), hepatocyte growth factor (HGF) and gastrin in the gastric cancer tissue , the surrounding mucosa and, for comparison, in the normal gastric mucosa, Furthermore, the luminal and plasma levels of gastrin in patients with gas tric cancer were determined, In addition, the gene and protein expressions of apoptosis-related proteins such as Bax and Bcl-2 were investigated by re verse transcription-polymerase chain reaction and Western blot. Twenty-five gastric cancer patients and 40 age- and gender-matched control subjects ho spitalized with non-ulcer dyspepsia were included into this study. Results: An overall H. pylori-seropositivity among gastric cancer patients was about 72% and was significantly higher than in the controls (56%). The prevalence of CagA-positive strains was also significantly higher among gas tric cancer patients than in controls (56% vs. 32%). The gene expression of HGF and TGF alpha was detected more frequently in gastric cancer tissue sa mples than in normal gastric mucosa (52% vs. 12% for HGF and 48% vs. 24% fo r TGF alpha). The extent of protein expression in Western blotting analysis for HGF and TGF alpha correlated with the mRNA expression of these factors . Gene expression of gastrin was detected in the antrum of all tested patie nts and in the majority (84%) of gastric cancer patients, The median plasma and luminal concentrations of gastrin in gastric cancer patients were sign ificantly higher than in controls, The gene expression of bcl-2 was detecte d in all (100%) and that of proapoptotic bax only in 56% of gastric cancer samples. In comparison to the surrounding non-tumorous tisssue, the gene ex pression of bax was significantly down-regulated and the gene expression of bcl-2 was up-regulated in gastric cancer tissue. At the protein level, Bax was not detectable and Bcl-2 was seen in 80% of gastric cancer samples. Conclusions: It is concluded that the patients infected with H. pylori, esp ecially with CagA-positive strains, are at a higher risk of developing a ga stric cancer. An increased production and release of gastrin, as well as an over-expression of growth factors such, as HGF and TGF alpha, might contri bute to the gastric carcinogenesis. In addition, a dysregulation of the Bax /Bcl-2 system with significant up-regulation of Bcl-2 is observed in gastri c cancer.