Cdx2 expression and its promoter methylation during metaplasia-dysplasia-carcinoma sequence in Barrett's esophagus

Makita, Kenji; Kitazawa, Riko; Semba, Shuho; Fujiishi, Koto; Nakagawa, Miku; Haraguchi, Ryuma; Kitazawa, Sohei

doi:10.3748/wjg.v19.i4.536

Cited by 12 publications

(9 citation statements)

References 11 publications

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“…2D), functional transcriptional activity of BOB.1 may have been lost or reduced by mechanisms other than epigenetic gene silencing. Indeed, similar phenomena, that genes once silenced by DNA hypermethylation of cancer cells can be significantly but transiently reactivated through chromatin remodeling without any changes in DNA methylation, have been described in several cell lines [16] and in the metaplasia-dysplasia-carcinoma sequence in the Barrett esophagus [13]. Therefore, when interpreting immunohistochemical results for diagnostic or research purposes, we must bear in mind that apparent positive immunostaining could merely be the result of chromatin remodeling [16] and that such transient expression often has little functional significance.…”

Section: Discussionmentioning

confidence: 93%

BOB.1-positive Classical Hodgkin’s Lymphoma Carries Hypermethylation of Its Promoter as Epigenetic Marker of Gene-silencing Memory

Watanabe

Kitazawa

Mizuno

et al. 2014

Acta Histochem. Cytochem

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Analysis of archival formalin-fixed, paraffin-embedded (FFPE) pathological specimens of three case of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) and three cases of classical Hodgkin lymphoma (CHL) revealed that hypermethylation of the BOB.1 gene promoter was exclusively observed in CHL. A discrepancy was observed, however, between the methylation status of the BOB.1 gene promoter and its expression in the EBV-positive mixed cellular CHL (MCCHL). Since MCCHL lacks the typical B-cell phenotype even in the presence of abundant BOB.1 transcription factors, functional activity of BOB.1 may be lost or reduced by a mechanism other than epigenetic gene silencing. When some tumor-suppressor gene products have lost their biological function, impact or significance of derepression of such genes may be little. Therefore, when interpreting immunohistochemical results for diagnostic or research purposes, it must be borne in mind that apparent positive immunostaining can merely be the result of chromatin remodeling and that such transient expression often has little functional significance. Any apparent positive immunohistochemical result needs to be interpreted carefully with the help of the hypermethylation status as a molecular marker of gene silencing memory.

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Section: Discussionmentioning

confidence: 93%

BOB.1-positive Classical Hodgkin’s Lymphoma Carries Hypermethylation of Its Promoter as Epigenetic Marker of Gene-silencing Memory

Watanabe

Kitazawa

Mizuno

et al. 2014

Acta Histochem. Cytochem

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“…It is believed that there is a close relationship between inflammatory responses and transcription factors since replacement of damaged tissues normally starts by cell proliferation. Subsequently, chronic inflammation can persuade unrestrained proliferation, which leads to the production of unwanted proteins as a result of CDX genes or even p53 gene (Makita et al, 2013). Since apoptosis is usually programmed by p53 to disregard death or abnormal cells in the cell cycle by binding to TNF receptors and Fas, any disruption in this pattern will results in unwanted cells.…”

Section: Discussionmentioning

confidence: 99%

Effect of probiotics on the expression of Barrett’s oesophagus biomarkers

Namin

Daryani

Mirshafiey

et al. 2015

Journal of Medical Microbiology

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Barrett's oesophagus (BO) is a complicated condition at the gastroesophageal junction in which normal squamous epithelium is changed to columnar and leads to oesophageal adenocarcinoma (OA). In the past decades, the prevalence of Barrett's disease and mortality rate of adenocarcinoma has significantly increased throughout the word. Data has shown that molecular pathogenesis of disease has not been clearly identified. However, a wide-range and successful administration of probiotics in cancer and gastrointestinal diseases has lead to the investigation into the possible inhibitory role of probiotics in oesophageal cancer. This study was conducted to evaluate the inhibitory effect of probiotics on the expression of biomarkers in an in vitro model. Two different Barrett's oesophageal cell lines were selected to co-culture with B. longum and Lactobacillus acidophilus to measure expression of IL-18, TNFa, p53 (tumour suppressor gene), cyclooxygenase 2 and CDX1 (caudal type homeobox 1) genes. In addition, two different aspects of probiotic administration, therapeutic and prophylactic test were also examined. Results showed that micro-organisms could inhibit expression of biomarkers and therapeutic culture conditions were more effective than prophylactic tests. The results obtained suggest that it is possible to incorporate the administration of probiotics in BO and OA prevention. INTRODUCTIONBarrett's oesophagus (BO) is well recognized as a precursor of oesophageal adenocarcinoma (OA), which is usually caused by gastroesophageal reflux disease (GORD). In BO, normal squamous epithelium is replaced by columnar intestinal epithelium because of GORD effects. It is known that progression of BO to OA includes sequence of metaplasia-dysplasia-adenocarcinoma, which is created by the effect of various factors and multiple pathways including environmental and genetic factors. The incidences of both Barrett's and oesophageal cancer have risen in the world particularly in the Western world and the UK by variation between 1/52 and 1/694, respectively (HvidJensen et al., 2011;Werner & Laßmann, 2012;Zimmerman, 2014). Subsequently, different studies have evaluated a range of putative factors that might support risk of progression of BO to OA. Current evidence suggests that progression of Barrett's disease is associated with the changes in bacterial population in GORD, BO and OA patients (Blackett et al., 2013). It has been suggested that Gram-negative bacteria (Lim & Fitzgerald, 2013;Sharma et al., 2013;Thrift et al., 2014). The use of probiotics has been established in the prevention of carcinogenic diseases. Probiotics are described as live micro-organisms applied in adequate amounts for beneficial use in order to strengthen the ordinary defence system and protect the gastrointestinal epithelium against pathogenic bacteria. Probiotics have been used successfully in cases of infant diarrhoea, food allergies, ulcerative colitis, colonic cancer, Crohn's disease and inflammatory bowel disease (Furrie et al., 2005;Steed et al., 2010;Ri...

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“…CXCL 1 and CXCL 3 play a role in spinal cord development by inhibiting the migration of oligodendrocyte precursors . CDX 1 and CDX 2 genes are essential for skeletal and intestinal development . These genes are usually expressed in the mucosal epithelium from the duodenum to the rectum, but one study demonstrated their presence in EAC tissue …”

Section: Normal Squamous Mucosa → Inflammation (Gerd) → Be Metaplasiamentioning

confidence: 99%

Epigenetics in the Pathogenesis of Esophageal Adenocarcinoma

Kailasam

Mittal

Agrawal

2014

Clinical Translational Sci

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Epigenetic influences, such as DNA methylation, histone acetylation and upregulation/downregulation of genes by microRNAs, change the genetic makeup of an individual without affecting DNA base pair sequences. Indeed, epigenetic changes play an integral role in the progression from normal esophageal mucosa to Barrett’s esophagus to esophageal adenocarcinoma via dysplasia- metaplasia-neoplasia sequence. Many genes involved in esophageal adenocarcinoma display hypermethylation, leading to their downregulation. The classes of these genes include cell cycle control, DNA and growth factor repair, tumor suppressors, anti-metastasis, WNT-related genes, and pro-apoptotic genes. Histone acetylation in the pathophysiology of esophageal diseases has not been thoroughly investigated, and its critical role in the development of esophageal adenocarcinoma is less defined. Many microRNAs have been associated with the development of Barrett’s esophagus and esophageal adenocarcinoma. Here, we critically addressed the specific steps most closely influenced by microRNAs in the progression from Barrett’s esophagus to esophageal adenocarcinoma. However, microRNAs can target up to hundreds of genes, making it difficult to correlate directly with a given phenotype of the disease. Esophageal adenocarcinoma progressing from pre-malignant condition of Barrett’s esophagus carries an extremely poor prognosis. Risk stratification for patients based on their epigenetic profiles may be useful in providing more targeted and directed treatment to patients.

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Cdx2 expression and its promoter methylation during metaplasia-dysplasia-carcinoma sequence in Barrett's esophagus

Abstract: Cdx2 expression is restored irrespective of the methylation status of its promoter. Apparent positive immunohistochemical results can be a molecular mark for gene silencing memory.

Cited by 12 publications

References 11 publications

BOB.1-positive Classical Hodgkin’s Lymphoma Carries Hypermethylation of Its Promoter as Epigenetic Marker of Gene-silencing Memory

BOB.1-positive Classical Hodgkin’s Lymphoma Carries Hypermethylation of Its Promoter as Epigenetic Marker of Gene-silencing Memory

Effect of probiotics on the expression of Barrett’s oesophagus biomarkers

Epigenetics in the Pathogenesis of Esophageal Adenocarcinoma

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