Gastrokine 1 expression in patients with and without Helicobacter pylori infection

Nardone, Gerardo; Rippa, Emilia; Martín, G; Rocco, Alba; Siciliano, Rosa Anna; Fiengo, Anna; Cacace, Giuseppina; Malorni, Antonio; Budillon, G; Arcari, Paolo

doi:10.1016/j.dld.2006.09.017

Cited by 47 publications

(53 citation statements)

References 46 publications

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“…Toback and colleagues reported that GKN1 protects the antral mucosa and promotes healing by facilitating restitution and proliferation after injury (3). Interestingly, GKN1 is downregulated in Helicobacter pylori-infected gastric epithelial cells, and the loss of GKN1 expression is detected in gastric cancer tissues and precancerous lesions such as intestinal metaplasia (4,5). We also witnessed frequent loss of GKN1 expression in gastric cancers and confirmed tumor suppressor activity of GKN1 through a functional analysis (6).…”

Section: Introductionmentioning

confidence: 58%

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GKN1–miR-185–DNMT1 Axis Suppresses Gastric Carcinogenesis through Regulation of Epigenetic Alteration and Cell Cycle

Yoon

Choi

et al. 2013

Clinical Cancer Research

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Purpose: Gastrokine 1 (GKN1) functions to protect the gastric antral mucosa and promotes healing by facilitating restoration and proliferation after injury. GKN1 is downregulated in Helicobacter pylori-infected gastric epithelial cells and loss of GKN1 expression is closely associated with gastric carcinogenesis, but underlying mechanisms of the tumor-suppressing effects of GKN1 remain largely unknown.Experimental Design: AGS, MKN1, MKN28 gastric cancer cells and HFE-145 immortalized nonneoplastic gastric mucosal cells were transfected with GKN1 or shGKN1. We conducted molecular and functional studies of GKN1 and miR-185 and investigated the mechanisms of alteration. We also analyzed epigenetic alterations in 80 gastric cancer tissues.Results: Restoration of GKN1 protein suppressed gastric cancer cell growth by inducing endogenous miR-185 that directly targets epigenetic effectors DNMT1 and EZH2 in gastric cancer cells. In addition, ectopic expression of GKN1 upregulated Tip60 and downregulated HDAC1 in an miR-185-independent manner, thereby inducing cell-cycle arrest by regulating cell-cycle proteins in gastric cancer cells. Notably, GKN1 expression was inversely correlated with DNMT1 and EZH2 expression in a subset of 80 gastric cancer tissues and various gastric cancer cell lines. Interestingly, it was found that GKN1 exerted a synergistic anticancerous effect with 5-fluorouracil on tumor cell growth, which suggests a possible therapeutic intervention method for gastric cancer.Conclusion: Our results show that GKN1 has an miR-185-dependent and -independent mechanism for chromatic and DNA epigenetic modification, thereby regulating the cell cycle. Thus, the loss of GKN1 function contributes to malignant transformation and proliferation of gastric epithelial cells in gastric carcinogenesis.

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Section: Introductionmentioning

confidence: 58%

“…containing the nuclei was resuspended in 50 mL of extraction buffer (20 mmol/L HEPES, pH 7.9, 420 mmol/L NaCl, 1.5 mmol/L Mgcl 2 , 0.2 mmol/L EDTA, and 10% glycerol) followed by incubation for 30 minutes at 4 C and collection of the nuclear extract by centrifugation.…”

Section: Translational Relevancementioning

confidence: 99%

GKN1–miR-185–DNMT1 Axis Suppresses Gastric Carcinogenesis through Regulation of Epigenetic Alteration and Cell Cycle

Yoon

Choi

et al. 2013

Clinical Cancer Research

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“…HP infection increases HSP27 expression (30,31). Because 46 of the 50 healthy individuals were infected with HP, the control group might also have had increased HSP expression in their sera due to HP infection.…”

Section: Discussionmentioning

confidence: 99%

“…Infection with HP is also associated with mucosal damage and increased stress production, leading to increased expression of HSP27 (30,31). Using the rapid urease test (RUT) (32), we determined that nine of the non-neoplastic mucosa tissues had HP infection, among these nine samples with HP infection were case 6 and five other cases (cases 9, 13, 21, 35, and 36), in which the paired non-neoplastic mucosa had higher HSP27 expression than the GA tissue.…”

Section: Discussionmentioning

confidence: 99%

Heat shock protein 27 is over-expressed in tumor tissues and increased in sera of patients with gastric adenocarcinoma

Huang¹,

Ye²,

Huang

et al. 2009

Clinical Chemistry and Laboratory Medicine

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Background: In a previous study, we found that heat shock protein 27 (HSP27) was over-expressed in gastric adenocarcinoma (GA) tissue. In this study, our goal was to further verify the expression profile of HSP27 in patients with GA. Methods: Western blot and immunohistochemistry were employed to determine HSP27 expression in 50 paired tumor and adjacent normal tissue. ELISA was used to quantify serum HSP27 concentrations in the same 50 GA patients and 50 healthy individuals. Results: Compared to adjacent normal tissues, HSP27 was over-expressed in 25 (50%, ps0.000) and 24 (48%, ps 0.000) cases of GA tissue by Western blot and immunohistochemistry, respectively. ELISA revealed significantly higher serum concentrations of HSP27 in patients with GA patients (means986 pg/mL) compared to healthy individuals (means573 pg/mL) (ps0.003). In addition, infection with Helicobacter pylori (HP) in healthy individuals was associated with increased expression of HSP27 in both gastric mucosa and serum. Conclusions: These data suggest that HSP27 is overexpressed in GA tissue and serum concentrations of HSP27 are increased in patients with GA. Over-expression of HSP27 may indicate a gastric malignant/infectious process. The detection of serum HSP27 concentrations by ELISA may be useful for screening for GA. Clin Chem Lab Med 2010;48:263-9.

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“…Therefore, GKN1 gene is transcriptional silenced in gastric cancer. Also GKN1 expression at protein level is reduced in patients owing H. pylori-positive chronic gastritis 7 and strongly downregulated or completely absent in patients with gastric cancer 8,9 . We observed that GKN1 down-regulation is one of the leading causes of gastric cancer (GC) development 7,9 .…”

Section: Introductionmentioning

confidence: 99%

Human Gastrokine 1 and its anti-amyloidogenic properties

Stadio¹,

Altieri²,

Minopoli³

et al. 2017

J Neurol Neuromedicine

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Gastrokine 1 (GKN1) is a 18 kDa stomach protein highly expressed in normal gastric tissue but absent in gastric cancer. GKN1 plays its major role in maintaining gastric mucosal integrity. Because of the presence in its central region of a BRICHOS domain, GKN1 is characterized by multifunctional properties since it interacts and regulates the activity of several proteins. The BRICHOS domain consists of about 100 amino acids and has been found in protein families often associated with major human diseases like familial British and Danish dementia (BRI2) or respiratory distress syndrome (surfactant protein C) (SP-C), both associated with amyloid formation. It has been shown that BRICHOS is a chaperon domain that has the property of binding precursor protein regions with high β-sheet tendencies, thereby preventing them from amyloid formation. Like the BRICHOS domains from BRI2 and SP-C precursor (proSP-C), also GKN1 is able to prevent fibrils formation of amyloidbeta peptide (Aβ) and to interact with the C-terminal region of APP thus hindering the γ-secretase proteolytic sites. Indeed, amyloid is of great medical importance since it originates in several major fatal diseases such as Alzheimer, Parkinson and diabetes mellitus. The results collected until now on the BRICHOS properties of GKN1 and those from other BRICHOS suggest that the different amyloids recognized by BRICHOS should contain similar structural elements therefore, the BRICHOS domain represents a potential powerfull tool for therapeutic approaches against amyloid associated diseases.

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Gastrokine 1 expression in patients with and without Helicobacter pylori infection

Cited by 47 publications

References 46 publications

GKN1–miR-185–DNMT1 Axis Suppresses Gastric Carcinogenesis through Regulation of Epigenetic Alteration and Cell Cycle

GKN1–miR-185–DNMT1 Axis Suppresses Gastric Carcinogenesis through Regulation of Epigenetic Alteration and Cell Cycle

Heat shock protein 27 is over-expressed in tumor tissues and increased in sera of patients with gastric adenocarcinoma

Human Gastrokine 1 and its anti-amyloidogenic properties

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