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E-cadherin Gene (e-cadherin + gene)
Selected AbstractsAnalysis of regulatory elements of E-cadherin with reporter gene constructs in transgenic mouse embryosDEVELOPMENTAL DYNAMICS, Issue 2 2003Marc P. Stemmler Abstract Proper regulation of E-cadherin,mediated cell adhesion is important during early embryonic development and in organogenesis. In mice, E-cadherin is expressed from the fertilized egg onward and becomes down-regulated during gastrulation in mesoderm and its derivatives, but its expression is maintained in all epithelia. E-cadherin promoter analyses led to the identification of binding sites for two transcriptional repressors, Snail and SIP1, which are able to mediate down-regulation in vitro, but little is known about the regulatory elements that govern E-cadherin transcriptional activity in vivo. Here, we compared the developmentally regulated expression of a series of lacZ -reporter transgenes fused to different sequences of the murine E-cadherin gene between ,6 kb, including the promoter, and +16 kb, covering one third of intron 2. Four different segments with distinct regulatory properties were identified. The promoter fragment from +0.1 to ,1.5 kb remains inactive in most cases but occasionally induces ectopic expression in mesodermal tissues, although it contains binding sites for the repressors Snail and SIP1. This promoter fragment also lacks positive elements needed for the activation of transcription in ectoderm and endoderm. Sequences from ,1.5 to ,6 kb harbor regulatory elements for brain-specific expression and, in addition, insulator or silencer elements, because they are consistently inactive in the mesoderm. Only if sequences from +0.1 to +11 kb are combined with the promoter fragments is E-cadherin,specific transgene expression observed in endoderm and certain epithelia. Sequences between +11 and +16 kb contain cis -active elements that generally enhance transcription. Our analyses show that E-cadherin expression is governed by a complex interplay of multiple regulatory regions dispersed throughout large parts of the locus. Developmental Dynamics 227:238,245, 2003. © 2003 Wiley-Liss, Inc. [source] E-cadherin abnormalities resulting from CPG methylation promoter in metastatic and nonmetastatic oral cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 1 2008Renato Vieira de Moraes MSc Abstract Background. This study aims to compare the alterations in the methylation profiles of E-cadherin in oral cancer, especially in tumors with lowest metatastic potential. Methods. Nine oral verrucous carcinomas (VCs), 20 oral well-differentiated squamous cell carcinomas without lymph node involvement (SCC-pN0), and 17 with lymph node involvement (SCC-pN+) were analyzed using methylation-specific polymerase chain reaction and immunohistochemical expression of E-cadherin gene. Results. The immunohistochemical expression of E-cadherin in VC was significantly higher (p = .016) when compared with SCC-pN0 and SCC-pN+ groups. The E-cadherin gene methylation was not correlated with its abnormal immunohistochemical expression in VC and SCC-pN0. All tumors of the SCC-pN+ group with unmethylated E-cadherin gene showed significant loss of E-cadherin immunoexpression (p = .044). Conclusions. The E-cadherin gene methylation presence in tumors with lowest invasive and metastatic potential, such as VC, suggests the early involvement of this epigenetic event in the multistep progression of the oral carcinogenesis. © 2007 Wiley Periodicals, Inc. Head Neck, 2008 [source] Hypermethylation in promoter region of E-cadherin gene is associated with tumor dedifferention and myometrial invasion in endometrial carcinomaCANCER, Issue 4 2003Ph.D., Tsuyoshi Saito M.D. Abstract BACKGROUND Loss of E-cadherin expression is associated with aberrant 5, CpG island methylation in various tumors. METHODS The authors analyzed the methylation status and immunohistochemical expression of E-cadherin in 142 endometrial tissues, consisting of 21 normal endometria, 17 endometrial hyperplasias, and 104 endometrial carcinomas. RESULTS All normal endometria and endometrial hyperplasias showed positive staining of E-cadherin, and methylation of the E-cadherin gene was not detected in any samples. In endometrial carcinoma, the positive ratio of methylation was higher and was associated with tumor dedifferention and myometrial invasion. In G1 endometrial adenocarcinomas, 66.7% showed positive staining and 33.3% showed heterogeneous staining. Methylation of the E-cadherin gene was detected in 15.6%. In G2 tumors, 19.0% showed positive staining, 69.0% showed heterogeneous staining and 11.9% showed negative staining. Methylation of the E-cadherin gene was found in 50.0%. In G3 tumors, 9.1% showed positive staining, 54.5% showed heterogeneous staining and 36.3% showed negative staining. Methylation of the E-cadherin gene was found in 81.8% of the tumors. Of the samples with no-myometrial invasion, 23.1% had methylation. In those with invasion in less than half of the myometrium, 28.6% did and in those with invasion of half or more of the myometrium, 55.6% had methylation. Of samples that did not have lymph node metastasis, 33.7% had methylation, whereas of samples that had lymph node metastasis, 60.0% had methylation. CONCLUSIONS This is the first report to analyze methylation of the E-cadherin gene promoter of endometrial carcinoma and the evidence suggests that methylation of the E-cadherin gene occurs in association with the acquisition of invasive capacity. Cancer 2003;97:1002,9. © 2003 American Cancer Society. DOI 10.1002/cncr.11157 [source] Cell adhesion system and human cancer morphogenesisCANCER SCIENCE, Issue 7 2003Setsuo Hirohashi Cell-cell adhesion determines the polarity of cells and participates in the maintenance of the cell societies called tissues. Cell-cell adhesiveness is generally reduced in human cancers. Reduced intercellular adhesiveness allows cancer cells to disobey the social order, resulting in destruction of histological structure, which is the morphological hallmark of malignant tumors. Reduced intercellular adhesiveness is also indispensable for cancer invasion and metastasis. A tumor-suppressor gene product, E-cadherin, and its undercoat proteins, catenins, which connect cadherins to actin filaments, are located at lateral borders, concentrating on adherens junctions, of epithelial cells and establish firm cell-cell adhesion. The E-cadherin cell adhesion system in cancer cells is inactivated by various mechanisms that reflect the morphological and biological characteristics of the tumor. Silencing of the E-cadherin gene by DNA hypermethylation around the promoter region occurs frequently, even in precancerous conditions. In diffuse infiltrating cancers, mutations are found in the genes for E-cadherin and ,-and ,-catenins. At the invading front of cancers, the E-cadherin cell adhesion system is inactivated by tyrosine phosphorylation of ,-catenin; an oncogene product, c- erb B-2 protein, is found to associate directly with ,-catenin. The E-cadherin cell adhesion system cross-talks with the Wingless/Wnt signaling pathway through ,-catenin, and expression of genes, which participate in cancer morphogenesis, may be regulated in conjunction with the Wingless/Wnt signaling pathway. Dysadherin, a newly identified cancer-associated cell membrane glycoprotein, down-regulates E-cadherin and promotes cancer metastasis. In conclusion, inactivation of the E-cadherin cell adhesion system by both genetic and epigenetic mechanisms plays a significant role during multistage human carcinogenesis. [source] Detecting methylation patterns of p16, MGMT, DAPK and E-cadherin genes in multiple myeloma patientsINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2010O. OZALP YUREGIR Summary Multiple myeloma (MM) is a B-cell neoplasia characterized by the clonal proliferation of plasma cells. Besides known genetic abnormalities, epigenetic changes are also known to effect MM pathogenesis. DNA methylation is an epigenetic mechanism that silences genes by adding methyl groups to cytosine-guanine dinucleotides at the promoter regions. In this study, the methylation status of four genes; p16, O6-methyl guanine DNA methyl transferase (MGMT), death-associated protein kinase (DAPK) and E-cadherin (ECAD); at the time of diagnosis was investigated using methylation-specific polymerase chain reaction (MS-PCR). In the 20 cases studied; methylation of the promoter regions of p16, MGMT, DAPK and ECAD genes was detected in 10%, 40%, 10% and 45% of the cases, respectively. In 65% (13/20) of cases, at least one of the genes studied had promoter methylation; while 35% of cases (7/20) had methylated promoters of more than one gene. There was a significant correlation between promoter hypermethylation of MGMT and the presence of extramedullary involvement; but for the other genes no correlation was found regarding disease properties like age, disease stage, clinical course and the presence of lytic bone lesions. Determining the methylation profiles of genes in MM, could lead to a new understanding of the disease pathogenesis and guide the assessment of treatment options. [source] | ||||||||||