Phenotype analysis by MUC2, MUC5AC, MUC6, and CD10 expression in Epstein-Barr virus-associated gastric carcinoma

Barua, Rita Rani; Uozaki, Hiroshi; Chong, Ja-Mun; Ushiku, Tetsuo; Hino, Rumi; Chang, Moon-Sung; Nagai, Hideo; Fukayama, Masashi

doi:10.1007/s00535-006-1841-y

Cited by 15 publications

(12 citation statements)

References 19 publications

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“…This expression profile (CLDN18+, 3‐) corresponds to that of normal gastric epithelium in adults and fetuses, but not to that of intestinal metaplasia (CLDN18‐, 3+). In accordance with CLDN expression patterns, almost half of the EBV‐associated GC cases demonstrated gastric‐type mucin expression (MUC5AC, MUC6), and the other half lacked gastric‐ or intestinal‐type mucin or CD10 expression 25 . In contrast, EBV‐negative GC comprised a heterogeneous group of four different CLDN phenotypes: gastric (CLDN18+, 3‐), intestinal (CLDN18‐, 3+), mixed (CLDN18+, 3+), and an undifferentiated type (CLDN18‐, 3‐) with variable expression patterns of mucin molecules.…”

Section: Ebv Infection and Development Of Carcinomasupporting

confidence: 57%

Epstein‐Barr virus and gastric carcinoma

Fukayama

2010

Pathology International

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Epstein-Barr virus (EBV) has been accepted as an infective agent causing gastric carcinoma (GC). Epstein-Barr virus-associated GC, comprising nearly 10% of all cases of GC, is the monoclonal growth of EBV-infected epithelial cells, which express several EBV-latent genes (latency I program). Sequential events in the gastric mucosa could be traced from EBV infection of the pit cells to fully developed carcinomas by EBV encoded small RNA (EBER)-in situ hybridization. The histological features of the carcinoma consist of a lace pattern of carcinoma cells within the mucosa and the dense infiltration of lymphocytes and macrophages at the invasive site, which might be due to cytokines produced by neoplastic cells. The primary molecular abnormality in EBV-associated GC is global and non-random CpG island methylation in the promoter region of many cancer-related genes. The experimental system of recombinant EBV infection using GC cell lines demonstrated that viral latent membrane protein 2A (LMP2A) is responsible for the promotion of DNA methylation. LMP2A up-regulates cellular DNMT1 through the phosphorylation of STAT3, causing CpG methylation of a tumor suppressor gene, PTEN. DNA methylation in EBV-infected stomach cells may be due to overdrive of the cellular defense against foreign DNA, which eventually leads to the development of EBV-associated GC.

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Section: Ebv Infection and Development Of Carcinomasupporting

confidence: 57%

Epstein‐Barr virus and gastric carcinoma

Fukayama

2010

Pathology International

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123

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“…EBV‐associated GC shows a low level of expression of keratin molecules (CK7, 18, and 19) ( 18 ) and has a null/gastric phenotype as determined by the expression pattern of mucin molecules (MUC5AC, MUC6). ( 19 ) These findings suggest that the targets of EBV infection and subsequent transformation are the precursor cells with intrinsic differentiation potential toward the gastric cell type but not the intestinal type.…”

Section: Ebv‐associated Gc Is Clinicopathologically a Distinct Subgromentioning

confidence: 90%

Epstein–Barr virus and gastric carcinoma: virus–host interactions leading to carcinoma

2008

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“…Gastric carcinoma (GC) is the second leading cause of cancer mortality in Eastern Asia and the world, accounting for approximately 10% of newly diagnosed cancers 1 . In addition to the established histological GC classification 2,3 and the mucin‐based GC classification, 4 we have proposed a novel GC phenotypic classification according to the type of claudin present in the GC, and including the following classifications: the gastric (G‐CLDN), intestinal (I‐CLDN), and unclassified claudin (U‐CLDN) phenotypes 5 . Claudins are a crucial component of tight junctions, which maintain epithelial cell polarity by acting as a diffusion barrier to the movement of proteins and lipids within the plasma membrane and form the primary barrier to paracellular transport of solutes across the cells 6–8 .…”

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confidence: 99%

Cdx2 transcription factor regulates claudin‐3 and claudin‐4 expression during intestinal differentiation of gastric carcinoma

Satake

Semba²,

Matsuda³

et al. 2008

Pathology International

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According to the expression of gastric (claudin-18) and intestinal claudins (claudin-3 and claudin-4), the authors have previously proposed a new phenotypic classification of gastric carcinoma (GC): the gastric (G-CLDN), intestinal (I-CLDN) and unclassified claudin (U-CLDN) phenotypes. The aim of the present study was to examine the role of Cdx2, the caudal-related transcription factor, on the regulation of intestinal claudins expression in vitro and in vivo. It was confirmed on immunohistochemistry that nonneoplastic gastric mucosa with intestinal metaplasia (IM) expressed Cdx2 with increased levels of intestinal claudin expression. In addition, Cdx2 expression was detected in 28 (30%) of 94 GC at the invasive front. Interestingly, Cdx2 expression had a significant association with the I-CLDN phenotype (P < 0.001), which was almost identical to the established gastric and intestinal mucin-based GC classification. Furthermore, the transfection of a recombinant human CDX2-expressing vector into TMK-1 (Cdx2-negative) GC cells specifically elevated the expression of claudin-3 and claudin-4 at the mRNA (CLDN3, 3.9-fold; CLDN4, 2.8-fold) and protein levels (claudin-3, 8.6-fold; claudin-4, 9.8-fold), whereas no induction of the other claudins was detected. These findings suggest that Cdx2 plays an important role in the regulation of intestinal claudin expression not only in gastric mucosa with IM but also GC.

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Phenotype analysis by MUC2, MUC5AC, MUC6, and CD10 expression in Epstein-Barr virus-associated gastric carcinoma

Cited by 15 publications

References 19 publications

Epstein‐Barr virus and gastric carcinoma

Epstein‐Barr virus and gastric carcinoma

Epstein–Barr virus and gastric carcinoma: virus–host interactions leading to carcinoma

Cdx2 transcription factor regulates claudin‐3 and claudin‐4 expression during intestinal differentiation of gastric carcinoma

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