Human gastrin mRNA expression up-regulated by Helicobacter pylori CagA through MEK/ERK and JAK2-signaling pathways in gastric cancer cells

Zhou, Jian; Xie, Yuan; Zhao, Yan; Wang, Shu; Liu, Yu

doi:10.1007/s10120-011-0044-2

Cited by 15 publications

(15 citation statements)

References 26 publications

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“…Consequently, the decline in the activity of FAK triggers a rearrangement of the cytoskeleton known as the hummingbird phenotype, characterized by elongation and spreading of host cells [54]. Furthermore, CagA participates in cell signaling by activating the PIK3CA and KRAS pathways [1], ERK (MAPK) [55, 56], and MEK/ERK and JAK1 signaling pathway in gastric cancer cells [57]. To our knowledge, there are no reports about the relationship to the CagA virulence factor and the expression of ANXA1 and Gal-1 anti-inflammatory proteins.…”

Section: Discussionmentioning

confidence: 99%

Expression of Annexin-A1 and Galectin-1 Anti-Inflammatory Proteins and mRNA in Chronic Gastritis and Gastric Cancer

Jorge

Mataruco

Araújo

et al. 2013

Mediators of Inflammation

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Objective. The anti-inflammatory proteins annexin-A1 and galectin-1 have been associated with tumor progression. This scenario prompted us to investigate the relationship between the gene and protein expression of annexin-A1 (ANXA1/AnxA1) and galectin-1 (LGALS1/Gal-1) in an inflammatory gastric lesion as chronic gastritis (CG) and gastric adenocarcinoma (GA) and its association with H. pylori infection. Methods. We analyzed 40 samples of CG, 20 of GA, and 10 of normal mucosa (C) by the quantitative real-time PCR (qPCR) technique and the immunohistochemistry assay. Results. High ANXA1 mRNA expression levels were observed in 90% (36/40) of CG cases (mean relative quantification RQ = 4.26 ± 2.03) and in 80% (16/20) of GA cases (mean RQ = 4.38 ± 4.77). However, LGALS1 mRNA levels were high (mean RQ = 2.44 ± 3.26) in 60% (12/20) of the GA cases, while low expression was found in CG (mean RQ = 0.43 ± 3.13; P < 0.01). Normal mucosa showed modest immunoreactivity in stroma but not in epithelium, while stroma and epithelium displayed an intense immunostaining in CG and GA for both proteins. Conclusion. These results have provided evidence that galectin-1 and mainly annexin-A1 are overexpressed in both gastritis and gastric cancer, suggesting a strong association of these proteins with chronic gastric inflammation and carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Expression of Annexin-A1 and Galectin-1 Anti-Inflammatory Proteins and mRNA in Chronic Gastritis and Gastric Cancer

Jorge

Mataruco

Araújo

et al. 2013

Mediators of Inflammation

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“…& Downregulation of JAK2 was reported to significantly suppress the proliferation of GC cells [42]. H. pylori-cytotoxin-associated protein A induces high mRNA expression of gastrin through the activation of JAK2 signaling pathway in GC cells, suggesting one potential cause of gastric carcinogenesis [43].…”

Section: Jak2 Amplificationmentioning

confidence: 99%

Molecular Classification of Gastric Adenocarcinoma: Translating New Insights from The Cancer Genome Atlas Research Network

Sunakawa

Lenz

2015

Curr. Treat. Options in Oncol.

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Gastric cancer is a heterogenous cancer, which may be classified into several distinct subtypes based on pathology and epidemiology, each with different initiating pathological processes and each possibly having different tumor biology. A classification of gastric cancer should be important to select patients who can benefit from the targeted therapies or to precisely predict prognosis. The Cancer Genome Atlas (TCGA) study collaborated with previous reports regarding subtyping gastric cancer but also proposed a refined classification based on molecular characteristics. The addition of the new molecular classification strategy to a current classical subtyping may be a promising option, particularly stratification by Epstein-Barr virus (EBV) and microsatellite instability (MSI) statuses. According to TCGA study, EBV gastric cancer patients may benefit the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) antibodies or phosphoinositide 3-kinase (PI3K) inhibitors which are now being developed. The discoveries of predictive biomarkers should improve patient care and individualized medicine in the management since the targeted therapies may have the potential to change the landscape of gastric cancer treatment, moreover leading to both better understanding of the heterogeneity and better outcomes. Patient enrichment by predictive biomarkers for new treatment strategies will be critical to improve clinical outcomes. Additionally, liquid biopsies will be able to enable us to monitor in real-time molecular escape mechanism, resulting in better treatment strategies.

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“…Current evidence suggests that the risk of gastric cancer is very low among persons harboring H pylori strains that lack the cag pathogenicity island. A relationship between gastrin and H pylori infections has shown that gastrin messenger RNA is up-regulated by H pylori –cytotoxin–associated protein A 81 . Beales and Calam 82 showed that infection of canine G cells with H pylori increased endogenous gastrin secretion from the G cells by 17%–27%.…”

Section: Expression Of Gastrin and The Cck-b Receptors In Gastric Canmentioning

confidence: 99%

Gastrin and Gastric Cancer

Smith

Nadella

Osborne

2017

Cellular and Molecular Gastroenterology and Hepatology

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Gastric cancer is the third leading cause of cancer-related mortality worldwide. Despite progress in understanding its development, challenges with treatment remain. Gastrin, a peptide hormone, is trophic for normal gastrointestinal epithelium. Gastrin also has been shown to play an important role in the stimulation of growth of several gastrointestinal cancers including gastric cancer. We sought to review the role of gastrin and its pathway in gastric cancer and its potential as a therapeutic target in the management of gastric cancer. In the normal adult stomach, gastrin is synthesized in the G cells of the antrum; however, gastrin expression also is found in many gastric adenocarcinomas of the stomach corpus. Gastrin’s actions are mediated through the G-protein–coupled receptor cholecystokinin-B (CCK-B) on parietal and enterochromaffin cells of the gastric body. Gastrin blood levels are increased in subjects with type A atrophic gastritis and in those taking high doses of daily proton pump inhibitors for acid reflux disease. In experimental models, proton pump inhibitor–induced hypergastrinemia and infection with Helicobacter pylori increase the risk of gastric cancer. Understanding the gastrin:CCK-B signaling pathway has led to therapeutic strategies to treat gastric cancer by either targeting the CCK-B receptor with small-molecule antagonists or targeting the peptide with immune-based therapies. In this review, we discuss the role of gastrin in gastric adenocarcinoma, and strategies to block its effects to treat those with unresectable gastric cancer.

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Human gastrin mRNA expression up-regulated by Helicobacter pylori CagA through MEK/ERK and JAK2-signaling pathways in gastric cancer cells

Cited by 15 publications

References 26 publications

Expression of Annexin-A1 and Galectin-1 Anti-Inflammatory Proteins and mRNA in Chronic Gastritis and Gastric Cancer

Expression of Annexin-A1 and Galectin-1 Anti-Inflammatory Proteins and mRNA in Chronic Gastritis and Gastric Cancer

Molecular Classification of Gastric Adenocarcinoma: Translating New Insights from The Cancer Genome Atlas Research Network

Gastrin and Gastric Cancer

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