Transformed immortalized gastric epithelial cells by virulence factor CagA of Helicobacter pylori through Erk mitogen-activated protein kinase pathway

Zhu, Yaping; Zhong, Xian; Zheng, Shu; Du, Qin; Xu, Weizhen

doi:10.1038/sj.onc.1208551

Cited by 56 publications

(43 citation statements)

References 53 publications

(45 reference statements)

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“…Similarly, CagA expression in gastric epithelial cells results in sustained ERK MAP kinase activation [23]. The research of Zhu et al [24] further confirms that the transformation of immortalized gastric epithelial cells is induced by CagA via the ERK/MAPK pathway. Activated ERK protein enters the cell nucleus to activate important tumor-related transcription factors such as AP1, CREB, NF I, NFjB, SP1, and myelocytomatosis viral oncogene homolog (MYC) [25].…”

Section: Discussionsupporting

confidence: 54%

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

et al. 2011

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Background Helicobacter pylori-cytotoxin-associated protein A (CagA) and gastrin are believed to play an important role in gastric carcinogenesis, but their interaction has been incompletely clear. Methods We constructed a eukaryotic expression vector pcDNA3.1/cagA and a luciferase reporter vector pGL/ gastrin promoter, and then co-transfected them into gastric cancer AGS and SGC-7901 cells. The two kinds of gastric cancer cells were, respectively, infected with cagA-positive H. pylori NCTC11637, and then the gastrin promoter activity and gastrin mRNA level were detected with a Dual-Luciferase reporter assay system and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. Next, after the MEK/ERK and JAK2-signaling pathway inhibitors, U0126 and AG490, were used to treat the two cell lines, or the ERK1 and JAK2 genes were knocked down by siRNAs (small interference RNAs) in the two cell lines, the gastrin promoter activity and gastrin mRNA level were observed again. Results The results indicated that CagA could activate the gastrin promoter and up-regulate gastrin mRNA expression in AGS and SGC-7901 cells, but these effects could be inhibited by the inhibitors U0126 and AG490, and the CagAinduced gastrin mRNA expression was down-regulated in the cells whose ERK1 or JAK2 gene was knocked down.

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Section: Discussionsupporting

confidence: 54%

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

et al. 2011

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“…Protein expression levels were measured for Bax, Bid, Bim and Puma (Bcl-2 pro-apoptotic members), and also for ERK1/2, p38, and JNK. Blots were reacted at 4 °C overnight with appropriate primary and secondary antibodies (Zhu et al, 2005).…”

Section: Western Blotmentioning

confidence: 99%

Cordycepin induces apoptosis by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules

Zhang

et al. 2010

J. Zhejiang Univ. Sci. B

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Abstract:Objective: To explore the molecular mechanism by which cordycepin inhibits cell proliferation and induces apoptosis of human colorectal cancer cells. Methods: Cell counting and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt) method were used to monitor the effects of cordycepin on cell proliferation. Flow cytometry (FCM) was used to analyze the effects of cordycepin on the cell cycle progress. Annexin V-fluorescein isothiocyanate (FITC) analysis was used to detect apoptosis at a very early stage. Caspase-Glo was used to determine caspase activity and Western blot was used to measure protein expression levels of c-Jun N-terminal kinase (JNK), p38, and Bcl-2 pro-apoptosis family. Results: The numbers of viable SW480 and SW620 cells and the proliferation of these cells were significantly reduced with increases in cordycepin concentration (P<0.01). The cell cycle progression of SW480 and SW620 was arrested at the G0/G1 phase by the addition of cordycepin, and apoptosis rates of cordycepin treatments were increased compared with the control group. Cordycepin-treated cells showed phosphatidylserine valgus, suggesting the existence of early apoptosis. Caspase-3/7 and -9 activity significantly increased and the protein expression levels of JNK, p38, and Bax, Bid, Bim, and Puma from Bcl-2 pro-apoptosis molecules also increased after the treatment with cordycepin. Conclusions: Cordycepin can inhibit SW480 and SW620 cell proliferation and induce apoptosis. Apoptosis might be induced by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules.

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“…This chronic gastritis can persist for decades and may result in nonresolving inflammation, which is a major driver of gastric cancer (6), and the interaction of host-pathogen contributes to this carcinogenesis (7). The protein CagA of H. pylori is closely associated with gastric cancer and can intervene in signal pathways in cells (8). To date, however, the underlying molecular mechanisms of carcinogenesis induced by H. pylori remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

FoxM1 is Overexpressed in Helicobacter pylori–Induced Gastric Carcinogenesis and Is Negatively Regulated by miR-370

Feng

Wang

Zeng

et al. 2013

Molecular Cancer Research

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Helicobacter pylori (H. pylori) infections are strongly implicated in human gastric mucosa-associated diseases. Forkhead box M1 (FoxM1), a key positive regulator of cell proliferation, is overexpressed in gastric cancer. MicroRNAs are important post-transcriptional regulators of gene expression. In this study, the effects of H. pylori infection on FoxM1 expression and possible mechanisms of carcinogenesis were explored. The expression of FoxM1 was gradually increased in human gastric specimens from inflammation to cancer. FoxM1 upregulation was time-and concentration-dependent in gastric epithelial-derived cell lines infected with H. pylori. CagA, a key virulence factor of H. pylori, was associated with increased FoxM1 expression.

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Transformed immortalized gastric epithelial cells by virulence factor CagA of Helicobacter pylori through Erk mitogen-activated protein kinase pathway

Cited by 56 publications

References 53 publications

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

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

Cordycepin induces apoptosis by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules

FoxM1 is Overexpressed in Helicobacter pylori–Induced Gastric Carcinogenesis and Is Negatively Regulated by miR-370

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