Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of the Ca(2+)-dependent, homotypic cell:cell adhesion molecule, E-cadherin (E-cad), suppresses tumor cell invasion and metastasis in experimental tumor models. Decreased E-cad expression is common in poorly differentiated, advanced-stage carcinomas. These data implicate E-cad as an "invasion suppressor" gene. The mechanism by which E-cad is silenced in advanced stage carcinomas is unclear. In this report, we show that: (a) the 5' CpG island of E-cad is densely methylated in E-cad-negative breast and prostate carcinoma cell lines and primary breast carcinoma tissue but is unmethylated in normal breast tissue; (b) treatment with the demethylating agent, 5-aza-2'-deoxycytidine, partially restores E-cad RNA and protein levels in E-cad-negative breast and prostate carcinoma cell lines; and (c) and E-cad promoter/CAT construct is expressed in both E-cad-positive and -negative breast and prostate carcinoma cell lines, indicating that these cells have the active transcriptional machinery necessary for E-cad expression. Our data demonstrate that frequent loss of E-cad expression in human breast and prostate carcinomas results from hypermethylation of the E-cad promoter region.
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PMID:E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. 758 73

The loss of epithelial differentiation in carcinomas, which is accompanied by increased mobility and invasiveness of the tumour cells, is often a consequence of reduced intercellular adhesion. Recent reports have indicated that the primary cause for the 'scattering' of the cells in invasive carcinomas is a disturbance of the integrity of intercellular junctions often involving the cell adhesion molecule E-cadherin. It has also been suggested that during invasion, carcinoma cells convert to a sort of mesenchymal stage, as do normal epithelial cells during development. Permanent and transient molecular mechanisms lead to the impairment of junction integrity of epithelial cells and thus to the progression of carcinomas towards a more invasive state.
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PMID:E-cadherin as an invasion suppressor. 758 28

We examined the expression and ligand specificity of the alpha 2 beta 1 integrin on human mammary epithelial cells (HMEC) and a panel of breast carcinoma cell lines in vitro. We found that the alpha 2 beta 1 integrin was universally, but quite variably expressed on these cells by FACS analysis. No significant correlation was observed between its expression and other known cellular phenotypes. Substrate attachment assays using blocking antibodies demonstrated that alpha 2 beta 1 integrin served as a receptor for collagen on HMEC and almost all breast carcinoma cells. However, its contribution to laminin binding of these cells appeared to be related to cellular differentiation as evaluated by sex steroid receptor status and by markers of epithelial-mesenchymal transition, i.e. loss of E-cadherin and expression of vimentin. Two different populations of non-malignant immortalized HMEC (184A1N4 and MCF-10A) contained cells capable of using alpha 2 beta 1 integrin as a laminin receptor. Breast cancer cell lines positive for estrogen receptor (ER) and E-cadherin (MCF-7, T47D, ZR75-1) could also use alpha 2 beta 1 integrin as a laminin receptor. Conversely, alpha 2 beta 1 integrin appeared to be incapable of binding to laminin or to be a very minor receptor for laminin on metastatic ER-negative breast carcinoma cells that expressed vimentin (MDA-MB 231, MDA-MB 435, and MDA-MB 436). These findings suggest that the ligand specificity of alpha 2 beta 1 integrin, i.e. its function as a laminin receptor, may be regulated during the malignant progression of breast carcinoma cells. A reduced contribution of alpha 2 beta 1 integrin to the cellular laminin binding appears to be associated with an increased malignant phenotype and with an epithelial-mesenchymal transition of breast carcinoma cells.
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PMID:Expression and ligand binding of alpha 2 beta 1 integrin on breast carcinoma cells. 760 85

Metastasis of colon carcinomas is assumed to be caused by multiple steps, which include a loss of cell adhesion that results in the release of carcinoma cells from the original tumor tissue. A human colon carcinoma cell line was established from a poorly differentiated metastatic adenocarcinoma without cell-cell adhesion and without expression of E-cadherin mRNA. To this cell line, mouse E-cadherin cDNA in a expression vector was co-transfected with a neomycin-resistant gene. The transfected cells, which expressed exogenous E-cadherin gene, showed a compact shape with strong cell-cell adhesion and with increased cell-substratum adhesion. These cells showed a significantly low anchorage independency and decreased invasiveness compared to the parental carcinoma cells. Their growth rate was decreased both in vitro and in the subcutis of nude mice.
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PMID:[Increased cell adhesiveness and decreased tumorigenicity induced in human colon carcinoma cells by transfection with E-cadherin cDNA]. 762 92

E-cadherin is a calcium dependent cell-cell adhesion molecule. In cancer tissue, detachment of the adhesion system is indispensable for invasion and metastasis of cancer cells. We have investigated mechanism of the dysfunction of E-cadherin-dependent cell-cell adhesion system in gastric carcinoma cells. Although the high expression of E-cadherin in a scirrhous gastric cancer cell line HSC-39, the function of E-cadherin was completely abolished. Western blotting of beta-catenin in HSC-39 cells demonstrated that a truncated beta-catenin was detected. The truncation was due to partial deletion of beta-catenin DNA. It was concluded that in HSC-39 loss of E-cadherin dependent cell-cell adhesion was due to mutation of beta-catenin gene.
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PMID:[Dysfunction of E-cadherin due to mutation of beta-catenin in a scirrhous gastric cancer cell line]. 762 93

Nineteen human pancreatic cancer cell lines were analyzed for possible abnormal mRNA and/or protein expression of the E-cadherin. Five lines showed no or markedly reduced expression of the E-cadherin, and protein was absent. In 9 lines, mRNA was positive but protein distribution was abnormal, i.e. diffusely positive in cytoplasm instead of membrane, or mixed distribution to membrane and cytoplasm. These 14 cell lines with abnormal E-cadherin expression grow in isolated fashion or loose sheet formation, indicating the loss of cell-cell adhesion system. These findings that the strong relation between E-cadherin abnormalities and loss of physical cell-cell interaction may explain the extensively poor prognosis of the patients with pancreatic carcinoma.
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PMID:[Abnormal expression of E-cadherin in human pancreatic carcinoma cell lines]. 762 94

E-cadherin has been identified as a tumor (invasion) suppressor gene, which is mutated in 50% of diffuse-type human gastric carcinomas. In other carcinomas, the expression of E-cadherin is down-regulated in the poorly differentiated cells such as from breast, bladder, lung and colon. We have here examined the in vivo properties of the genomic E-cadherin promoter in well and poorly differentiated carcinoma cell lines in order to gain insights into the mechanisms of E-cadherin down-regulation in tumors. In vivo footprinting analysis revealed that positive regulatory elements of the E-cadherin promoter (a GC-rich region, the CCAAT-box and a palindromic element) are specifically bound by transcription factors in E-cadherin-expressing but not in non-expressing cells. The tested cell systems include more than a dozen carcinomas cell lines as well as mammary epithelial cells where E-cadherin expression can be switched off by activation of a Fos-estrogen receptor fusion protein and rhabdomyosarcoma cells where E-cadherin expression was induced by transfection with E1A. Mapping of DNase I hypersensitive sites showed that the chromatin structure in the promoter region is loosened in expressing but condensed in non-expressing cells. Furthermore, the endogenous E-cadherin promoter is specifically methylated at CpG sites in the undifferentiated cells. We also show that the in vivo properties of the promoter in E-caherin-negative carcinoma cells are similar as in mesenchymal cells, i.e. fibroblasts or sarcoma cells. These data suggest that silencing of the E-cadherin promoter during epithelialmesenchymal transition and tumor progression is due to a loss of factor binding in vivo and to chromatin rearrangement in the regulatory region.
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PMID:Progression of carcinoma cells is associated with alterations in chromatin structure and factor binding at the E-cadherin promoter in vivo. 763 Jun 31

HECD-1 monoclonal antibody has been used to localize E-cadherin, a calcium-dependent cell-cell adhesion molecule, in microwave-treated, paraffin-embedded sections from 53 cases of cervical intraepithelial neoplasia (CIN) (11 CIN I, 22 CIN II, and 20 CIN III), 16 invasive cervical squamous cell carcinomas, and seven metastases. In normal cervix, E-cadherin was expressed on the cell membrane of basal and parabasal cells. Cytoplasmic staining was present in occasional basal cells only. In CIN, the presence and localization of cytoplasmic E-cadherin were found to be significantly correlated with the grade of the CIN lesion. In squamous cell carcinomas, reduced membranous and increased cytoplasmic staining was seen with worsening differentiation. Loss of membranous E-cadherin expression was also detected in 4/7 metastatic deposits. E-cadherin expression (120 kD form on Western blotting) was seen in human cervical carcinoma cell lines (HT3, ME180, C4I, Caski) that maintained the ability to aggregate in a homotypic adhesion assay and showed a typical epithelial morphology. E-cadherin-negative cell lines (Hela, SiHa, C33A) did not show adhesion. HOG-1 was the only E-cadherin-negative cell line which showed a significant degree of cell-cell aggregation. These data indicate that loss of membranous E-cadherin expression may represent one of the abnormalities underlying loss of cell polarity and differentiation which characterize CIN and invasive cervical cancer.
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PMID:Altered expression and function of E-cadherin in cervical intraepithelial neoplasia and invasive squamous cell carcinoma. 763 25

We examined immunohistochemically the expression of E-cadherin which is Ca2+ dependent intercellular adhesion molecules in bladder carcinoma and investigated the correlation among the expression of E-cadherin, pathological examination, clinical findings and course. Fifty cases of bladder carcinoma were examined except one squamous cell carcinoma. The pattern of the immunohistochemical staining by E-cadherin antibody were classified into 4 groups as follows. The tumor, over 75% of which cells were stained like normal epithelium, was regarded as (2+). When from 50% to 75% of the carcinoma cells were stained, it was (+). When from 25% to 50% of the carcinoma cells were stained, it was (+/-). The tumor showing that under 25% of the cells were stained or lack of staining was regarded as (-). It was demonstrated that the percentage of positive staining was significantly lower in cases of high grade or high stage tumors compared with those of low grade or low stage. As the pattern of invasion, 88% of the cases showing INF alpha was observed as (2+) or (+), while all cases with INF gamma showed (+/-) or (-). The patients with superficial tumors showing (+/-) or (-) tended to have the higher local recurrence rate of the carcinoma compared with those showing (2+) or (+) staining. Immunoblotting analysis demonstrated no evidence of gross alteration of E-cadherin molecules between normal and carcinoma cells of the bladder. In conclusion, the decrease of E-cadherin expression may contribute to the tumor grade and invasiveness of bladder carcinoma.
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PMID:[The expression of the E-cadherin in human urinary bladder carcinoma]. 763 35

The tyrosine kinase substrate p120cas (CAS), which is structurally similar to the cell adhesion proteins beta-catenin and plakoglobin, was recently shown to associate with the E-cadherin-catenin cell adhesion complex. beta-catenin, plakoglobin, and CAS all have an Arm domain that consists of 10 to 13 repeats of a 42-amino-acid motif originally described in the Drosophila Armadillo protein. To determine if the association of CAS with the cadherin cell adhesion machinery is similar to that of beta-catenin and plakoglobin, we examined the CAS-cadherin-catenin interactions in a number of cell lines and in the yeast two-hybrid system. In the prostate carcinoma cell line PC3, CAS associated normally with cadherin complexes despite the specific absence of alpha-catenin in these cells. However, in the colon carcinoma cell line SW480, which has negligible E-cadherin expression, CAS did not associate with beta-catenin, plakoglobin, or alpha-catenin, suggesting that E-cadherin is the protein which bridges CAS to the rest of the complex. In addition, CAS did not associate with the adenomatous polyposis coli (APC) tumor suppressor protein in any of the cell lines analyzed. Interestingly, expression of the various CAS isoforms was quite heterogeneous in these tumor cell lines, and in the colon carcinoma cell line HCT116, which expresses normal levels of E-cadherin and the catenins, the CAS1 isoforms were completely absent. By using the yeast two-hybrid system, we confirmed the direct interaction between CAS and E-cadherin and determined that CAS Arm repeats 1 to 10 are necessary and sufficient for this interaction. Hence, like beta-catenin and plakoglobin, CAS interacts directly with E-cadherin in vivo; however, unlike beta-catenin and plakoglobin, CAS does not interact with APC or alpha-catenin.
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PMID:The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin. 765 99


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