Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic atrophic gastritis can be induced either by H. pylori or by an autoimmune process. The protein product of bcl-2, which is a protooncogene, blocks apoptosis. Aberrant bcl-2 expression has been found in 68% of atrophic gastritis patients. The aim of this study was to compare bcl-2 expression in 20 autoimmune atrophic gastritis patients to that in 20 H. pylori-associated atrophic gastritis patients. Twenty patients with H. pylori antral gastritis but without atrophy served as controls. The bcl-2 expression was assessed by immunohistochemical staining of gastric biopsies, using mouse anti-human bcl-2 monoclonal antibodies. Autoimmune atrophic gastritis patients were younger, mainly females, with a significantly higher serum gastrin level than the H. pylori-associated atrophic gastritis group (P < 0.001). The bcl-2 was expressed in 10/20 (50%) of autoimmune atrophic gastritis patients, in 9/20 (45%) of H. pylori-associated atrophic gastritis patients (P = 0.73), and in 2/20 (10%) of controls. There was no correlation between bcl-2 expression and the presence of intestinal metaplasia (P = 0.35). Our findings confirm that H. pylori-associated atrophic gastritis and autoimmune atrophic gastritis are two different conditions, but with equal expression of bcl-2. Excessive expression of bcl-2 is found only in atrophic gastritis, but not in H. pylori antral gastritis without atrophy.
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PMID:Expression of bcl-2 in autoimmune and Helicobacter pylori-associated atrophic gastritis. 1021 22

This study investigated sonic hedgehog (Shh) signalling in gastric metaplasia in the insulin-gastrin (InsGas) hypergastrinaemic mouse +/- Helicobacter felis (H. felis) infection. Sonic hedgehog gene and protein expression was reduced in pre-metaplastic lesions from non-infected mice (90% gene reduction, P<0.01) compared to normal mucosa. Sonic hedgehog was reactivated in gastric metaplasia of H. felis-infected mice (3.5-fold increase, P<0.01) compared to pre-metaplastic lesions. Additionally, the Shh target gene, glioma-associated oncogene (Gli)-1, was significantly reduced in the gastric glands of InsGas mice (75% reduction, P<0.05) and reactivated with H. felis infection (P<0.05, base of glands, P<0.01 stroma of metaplastic glands). The ability of H. felis to activate the Shh pathway was investigated by measuring the effect of target cytokine, interleukin-8 (IL-8), on Shh expression in AGS and MGLVA1 cells, which was shown to induce Shh expression at physiological concentrations. H. felis induced the expression of NF-kappaB in inflammatory infiltrates in vivo, and the expression of the IL-8 mouse homologue, protein KC, in inflammatory infiltrates and metaplastic lesions. Sonic hedgehog pathway reactivation was paralleled with an increase in proliferation of metaplastic lesions (15.75 vs 4.39% in infected vs non-infected mice, respectively, P<0.001). Furthermore, Shh overexpression increased the growth rate of the gastric cancer cell line, AGS. The antiapoptotic protein, bcl-2, was expressed in the stroma of infected mice, along with a second Shh target gene, patched-1 (P=0.0001, stroma of metaplastic gland). This study provides evidence suggesting reactivation of Shh signalling from pre-metaplastic to advanced metaplastic lesions of the stomach and outlines the importance of the Shh pathway as a potential chemoprophylactic target for gastric carcinogenesis.
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PMID:De-regulation of the sonic hedgehog pathway in the InsGas mouse model of gastric carcinogenesis. 1750 14

Elevated serum concentrations of the hormone gastrin are associated with the development of gastric carcinoid tumors, but the mechanisms of tumor development are not fully understood. We hypothesized that the antiapoptotic effects of gastrin may be implicated and have therefore investigated the role of antiapoptotic members of the bcl-2 family of proteins. AGS-G(R) human gastric carcinoma cells stably transfected with the CCK-2 receptor were used to assess changes in the expression of bcl-2 family members following gastrin treatment and the function of mcl-1 during apoptosis was investigated by use of small-interfering RNA (siRNA). Treatment of AGS-G(R) cells with 10 nM gastrin for 6 h caused maximally increased mcl-1 protein abundance. Gastrin-induced mcl-1 expression was inhibited by the transcription inhibitor actinomycin D and by the protein synthesis inhibitor cycloheximide. Downstream signaling of mcl-1 expression occurred via the CCK-2 receptor, protein kinase C, and MAP kinase pathways, but not via PI 3-kinase. Transfection with mcl-1 siRNA significantly suppressed mcl-1 protein expression and abolished the antiapoptotic effects of gastrin on serum starvation-induced apoptosis. Mcl-1 protein expression was also specifically increased in the type I enterochromaffin-like cell carcinoid tumors of 10 patients with autoimmune atrophic gastritis and hypergastrinemia. Gastrin therefore signals via the CCK-2 receptor, protein kinase C, and MAP kinase to induce expression of antiapoptotic mcl-1 in AGS-G(R) cells, and mcl-1 expression is also increased in human hypergastrinemia-associated type I gastric carcinoid tumors. Gastrin-induced mcl-1 expression may therefore be an important mechanism contributing toward type I gastric carcinoid development.
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PMID:Gastrin increases mcl-1 expression in type I gastric carcinoid tumors and a gastric epithelial cell line that expresses the CCK-2 receptor. 1871 2

Gastroesophageal malignancies are highly aggressive tumors with mortality rates remaining close to incidence rates; the majority of patients have advanced incurable disease at diagnosis. Although patients receive palliative benefit from chemotherapy, 5-year survival rates remain dismally low. In the past few decades, significant progress in understanding tumor biology has led to development of therapies that target critical aspects of the oncogenic pathway. Such targets include cell growth regulators (human epidermal growth factor like receptor, Ki-67), vascular modulators (vascular endothelial growth factor), cell cycle checkpoint modulators (p16, p21, cyclin D1, cyclindependent kinases), apoptosis promoters (p53, bax, bcl-2), and cell proliferators, tissue invasion and metastasis potentiators (matrix metalloproteinase, E-cadherin, gastrin 17). Clinical assessment of the inhibition of some of these targets is under way in various tumor types, including gastroesophageal cancers. This paper reviews emerging data on selected molecular targets and their antitumor potential in gastroesophageal malignancies.
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PMID:Incorporation of biologic therapies in the management of gastroesophageal cancers. 1934 57