A gene encoding an apurinic/apyrimidinic endonuclease-like protein is up-regulated in human gastric cancer

Wang, Gang-Shi; Wang, Mengwei; Wu, Bing; Liu, Xiaobing; Wang, You; Yang, Xinyan

doi:10.3748/wjg.v9.i6.1196

Cited by 8 publications

(10 citation statements)

References 44 publications

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“…We have identified a critical protective role of APE-1 acetylation in Bax-mediated GEC apoptosis by H. pylori . As there are some reports that APE-1 levels are altered in gastric neoplasia,41, 42 our finding that H. pylori infection enhances APE-1 acetylation in gastric epithelial cells suggests that the acetylation status of APE-1 may influence development of gastric cancer. Future studies are required to assess how mutation of APE-1 at its N-terminal Lys residues causes mitochondrial translocation of Bax and induction of host cell apoptosis to prevent potential loss of their niche thereby increasing the opportunity to permit chronic or persistent infection.…”

Section: Discussionsupporting

confidence: 51%

Acetylation of Apurinic/Apyrimidinic Endonuclease-1 Regulates Helicobacterpylori-Mediated Gastric Epithelial Cell Apoptosis

et al. 2009

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BACKGROUND & AIMS-Helicobacter pylori-induced gastric epithelial cell (GEC) apoptosis is a complex process that includes activation of the tumor suppressor p53. p53-mediated apoptosis involves p53 activation, bax transcription and cytochrome c release from mitochondria. Apurinic/ apyrimidinic endonuclease-1 (APE-1) regulates transcriptional activity of p53: H. pylori induce APE-1 expression in human GEC. H. pylori infection increases intracellular calcium ion concentration [Ca 2+ ] i of GEC, which iinduces APE-1 acetylation. We investigated the effects of H. pylori infection and APE-1 acetylation on GEC apoptosis.

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Section: Discussionsupporting

confidence: 51%

Acetylation of Apurinic/Apyrimidinic Endonuclease-1 Regulates Helicobacterpylori-Mediated Gastric Epithelial Cell Apoptosis

et al. 2009

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“…Previously, we reported that treatment with hydrogen peroxide as well as infection with H. pylori, but not Campylobacter jejuni, enhanced APE-1/Ref-1 expression in human gastric epithelial cells (32). Moreover, altered levels or cellular location of APE-1/Ref-1 have been found in some cancers, including ovarian and prostate (33,34), while an APE-1/Ref-1-like gene was recently shown to be up-regulated in gastric cancer (35).…”

Section: Interleukin-8 Induction By Helicobacter Pylori In Gastric Epmentioning

confidence: 99%

“…Furthermore, APE-1/Ref-1 itself is regulated by ROS and other environmental stimuli (25,26,28,61), and it has been suggested that the induction of IL-8 and other chemokines by H. pylori is redox sensitive and may depend on ROS-mediated activation of NF-B and AP-1 in gastric epithelial cells (17). Interestingly, an APE-1/Ref-1-like gene has been associated with gastric cancer (35) and H. pylori itself has been implicated in gastric carcinogenesis (2,62). Taken together, we believe that APE-1/Ref-1 plays a unique role in sensing oxidative stress and coordinating molecular events ranging from DNA repair and transcription factor regulation.…”

Section: Ape-1/ref-1 Is Involved In Il-8 Promoter Activationmentioning

confidence: 99%

Interleukin-8 Induction by Helicobacter pylori in Gastric Epithelial Cells is Dependent on Apurinic/Apyrimidinic Endonuclease-1/Redox Factor-1

O'Hara

Bhattacharyya

Mifflin³

et al. 2006

The Journal of Immunology

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Helicobacter pylori infection causes inflammation and increases the expression of IL-8 in human gastric epithelial cells. H. pylori activates NF-κB and AP-1, essential transcriptional factors in H. pylori-induced IL-8 gene transcription. Although colonization creates a local oxidative stress, the molecular basis for the transition from infection to the expression of redox-sensitive cytokine genes is unknown. We recently reported that the expression of apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE-1/Ref-1), which repairs oxidative DNA damage and reductively activates transcription factors including AP-1 and NF-κB, is increased in human gastric epithelia during H. pylori infection. In this study, we examine whether APE-1/Ref-1 functions in the modulation of IL-8 gene expression in H. pylori-infected human gastric epithelial cells. Small interfering RNA-mediated silencing of APE-1/Ref-1 inhibited basal and H. pylori-induced AP-1 and NF-κB DNA-binding activity without affecting the nuclear translocation of these transcription factors and also reduced H. pylori-induced IL-8 mRNA and protein. In contrast, overexpression of APE-1/Ref-1 enhanced basal and H. pylori-induced IL-8 gene transcription, and the relative involvement of AP-1 in inducible IL-8 promoter activity was greater in APE-1/Ref-1 overexpressing cells than in cells with basal levels of APE-1/Ref-1. APE-1/Ref-1 inhibition also reduced other H. pylori-induced chemokine expression. By implicating APE-1/Ref-1 as an important regulator of gastric epithelial responses to H. pylori infection, these data elucidate a novel mechanism controlling transcription and gene expression in bacterial pathogenesis.

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“…Our previous study [22] identified an upregulated transcript, named gastric cancer related gene 213 (GCRG213), in human gastric adenocarcinoma. BLAST analysis of GCRG213 sequence indicated 88% homology with human LI and revealed a putative conserved domain, apurinic/apyrimidinic endonucleas1 (APE), in GCRG213-ORF.…”

Section: Introductionmentioning

confidence: 99%

Expression of a LINE-1 endonuclease variant in gastric cancer: its association with clinicopathological parameters

et al. 2013

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BackgroundLong interspersed nuclear element-1 (LINE-1 or L1), the most abundant and only autonomously active family of non-LTR retrotransposons in the human genome, expressed not only in the germ lines but also in somatic tissues. It contributes to genetic instability, aging, and age-related diseases, such as cancer. Our previous study identified in human gastric adenocarcinoma an upregulated transcript GCRG213, which shared 88% homology with human L1 sequence and contained a putative conserved apurinic/apyrimidinic endonucleas1 domain.MethodsImmunohistochemistry was carried out by using a monoclonal mouse anti-human GCRG213 protein (GCRG213p) antibody produced in our laboratory, on tissue microarray constructed with specimens from 175 gastric adenocarcinoma patients. The correlation between GCRG213p expression and patient clinicopathological parameters was evaluated. GCRG213p expression in gastric cancer cell lines were studied using Western blotting analysis. L1 promoter methylation status of gastric cancer cells was tested using methylation-specific PCR. BLASTP was used at the NCBI Blast server to identify GCRG213p sequence to any alignments in the Protein Data Bank databases.ResultsMost primary gastric cancer, lymph node metastases and gastric intestinal metaplasia glands showed positive GCRG213p immunoreactivity. High GCRG213p immunostaining score in the primary gastric cancer was positively correlated with tumor differentiation (well differentiated, p = 0.001), Lauren’s classification (intestinal type, p < 0.05) and a late age onset of gastric adenocarcinoma (≥65 yrs; p < 0.05). GCRG213p expression has no association with other clinicopathological parameters, including survival. Western blotting analysis of GCRG213p expression in gastric cancer cells indicated that GCRG213p level was higher in gastric cancer cell lines than in human normal gastric epithelium immortalized cell line GES-1. Partial methylation of L1 in gastric cancer cells was confirmed by methylation-specific PCR. BLASTP program analysis revealed that GCRG213p peptide shared 83.0% alignment with the C-terminal region of L1 endonuclease (L1-EN). GCRG213p sequence possesses the important residues that compose the conserved features of L1-EN.ConclusionsGCRG213p could be a variant of L1-EN, a functional member of L1-EN family. Overexpression of GCRG213p is common in both primary gastric cancer and lymph node metastasis. These findings provide evidence of somatic L1 expression in gastric cancer, and its potential consequences in the form of tumor.

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A gene encoding an apurinic/apyrimidinic endonuclease-like protein is up-regulated in human gastric cancer

Cited by 8 publications

References 44 publications

Acetylation of Apurinic/Apyrimidinic Endonuclease-1 Regulates Helicobacterpylori-Mediated Gastric Epithelial Cell Apoptosis

Acetylation of Apurinic/Apyrimidinic Endonuclease-1 Regulates Helicobacterpylori-Mediated Gastric Epithelial Cell Apoptosis

Interleukin-8 Induction by Helicobacter pylori in Gastric Epithelial Cells is Dependent on Apurinic/Apyrimidinic Endonuclease-1/Redox Factor-1

Expression of a LINE-1 endonuclease variant in gastric cancer: its association with clinicopathological parameters

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