Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:B0FTZ7 (catenin)
 18,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

E-cadherin is crucial to the intercellular adherens junctions which are involved in the organisation and maintenance of epithelial structure and suppression of tumour invasion. E-cadherin is associated with the actin cytoskeleton via cytoplasmic proteins, including alpha-, beta- and gamma-catenins, which together form the cadherin/catenin complex. To evaluate changes of the molecules of the cadherin/catenin complex in colorectal carcinogenesis, seventy-four sporadic adenomas, samples of histologically normal epithelium adjacent to 65 adenomas, and 52 carcinomas arising in adenomas were investigated by immunohistochemistry. All normal epithelial cells showed a uniform membranous staining pattern for E-cadherin, alpha-, beta-, and gamma-catenin. Decreased expression of all 4 proteins occurred in parallel in adenomas and carcinomas (in all cases, p < 10(-5). Decreased expression of the cadherin/catenin complex in adenomas was associated with increasing severity of dysplasia (p < 0.001, for E-cadherin, alpha-, and gamma-catenin, p < 0.005 for beta-catenin). Carcinomas displayed significantly reduced expression of the cadherin/catenin complex compared with their associated adenomas (all p < 0.001). The results directly confirm that colorectal tumour progression and invasion is associated with disruption of the cadherin/catenin complex and suggest that the genetic changes and transcriptional modulation of catenins underlying this progression may affect all members of the complex.
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PMID:Reduced expression of molecules of the cadherin/catenin complex in the transition from colorectal adenoma to carcinoma. 921 95

The immunocytochemical expression of cadherins and catenins was examined during the process of oral carcinogenesis by comparing their expression in normal and dysplastic epithelium with primary and metastatic carcinomas. While control epithelium showed normal distribution for P and E cadherin and the catenins, in severe dysplasia P-cadherin was upregulated. In other cases and in carcinoma-in-situ adjacent to infiltrating carcinomas, membranous expression of the cadherins and catenins was reduced or lost. The changes in expression of E-cadherin and the catenins suggest that disruption of the E-cadherin/catenin complex is a late event associated with invasion. In primary carcinomas reduced membranous and cytoplasmic staining were observed for both cadherins and catenins. Abnormal localisation of E-cadherin occurred in the more superficial parts of the better differentiated carcinomas, suggesting abnormality to the E-cadherin complex(es). In contrast, membranous expression of cadherins and catenins was reduced or lost in the deep invasive margin of primary carcinomas and in most poorly differentiated carcinomas. For E-cadherin at least, this reduction appears associated with differentiation, invasion and possibly prognosis. Possible mechanisms involved for changes in expression of the cadherins and associated catenins and areas for further study are discussed.
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PMID:Expression of cadherins and catenins in oral epithelial dysplasia and squamous cell carcinoma. 972 68

Loss of expression and function of the E-cadherin/catenin membrane complex can result in loss of cell adhesion and contribute to invasive or metastatic potential in carcinomas. The aim of this study was to examine the expression of alpha- and beta-catenin and E-cadherin in Barrett's esophagus with and without dysplasia and in esophageal adenocarcinomas and to identify any relationship with tumor growth pattern and clinical outcome. Immunoperoxidase staining for alpha- and beta-catenin and E-cadherin was performed on specimens of Barrett's esophagus with and without dysplasia and on 54 esophageal adenocarcinoma specimens. Membranous staining for all of the components was seen in normal gastric and esophageal mucosa. Abnormal expression of beta-catenin, alpha-catenin, and E-cadherin was significantly associated with higher degrees of dysplasia in Barrett's esophagus. Fourteen of 16 cases of high grade dysplasia and 7 of 7 cases of intramucosal carcinoma showed abnormal expression of beta-catenin, compared with 3 of 6 cases indefinite for dysplasia and 11 of 17 cases with low grade dysplasia (P = 0.022). Similar results were seen for expression of alpha-catenin (P < .01) and E-cadherin (P = .049). In esophageal adenocarcinomas, preserved expression of these proteins occurred more frequently in well-differentiated tumors; abnormal expression was more common in diffusely infiltrative poorly differentiated tumors that did not form glands. Focal nuclear staining for beta-catenin was present in two high-grade dysplasias, two intramucosal carcinomas, and five adenocarcinomas. No survival advantage was demonstrated for patients whose tumors retained expression of these cell adhesion components. In conclusion, abnormal expression of the E-cadherin/catenin membrane complex is common in esophageal adenocarcinoma and occurs early in the dysplasia/carcinoma sequence in Barrett's esophagus, indicating that disturbances in this cell adhesion complex might be important in tumorigenesis and tumor progression in this disorder.
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PMID:Expression of beta-catenin, alpha-catenin, and E-cadherin in Barrett's esophagus and esophageal adenocarcinomas. 975 59

Maintenance of an adhesive function for cadherins requires appropriate membranous cellular expression and intact cadherin-catenin complexes. In normal squamous mucosa of the oesophagus there is membranous co-expression of E- and P-cadherin (E-cad, P-cad) in the basal compartment, whereas suprabasal stratification is associated with preservation of E-cad expression but loss of P-cad. Immunohistochemical staining of squamous dysplasia/carcinoma in situ shows a striking increase in the proportion of cells within the epithelial compartment showing co-expression of E- and P-cad with strong appropriate membranous expression of beta and gamma catenin. Strong membranous co-expression of E- and P-cad and beta catenin is seen on keratinocytes at the periphery of islands of invasive better-differentiated squamous carcinoma with keratinisation, mimicking normal mucosa. Beta catenin may be phosphorylated with implied loss of cadherin binding. Membranous cadherin and catenin expression is significantly down-regulated in poorly differentiated squamous carcinoma. No beta catenin mutations were demonstrated in squamous carcinomas following DNA extraction and sequencing, nor was any nuclear cadherin seen. Changes in cadherin-catenin complexes with cellular phenotype is well demonstrated in spindle cell carcinomas with a shift of cadherin expression from membranous to cytoplasmic between the epithelioid and spindle cell components of the tumour and with loss of expression in the sarcomatoid elements. In conclusion, we demonstrate an increased expression of P-cadherin early in tumourigenesis with loss of cadherin-catenin complexes in poorly differentiated invasive carcinomas. Cadherin/catenin expression may govern both the phenotype and biology of oesophageal squamous carcinomas.
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PMID:Sequential changes in cadherin-catenin expression associated with the progression and heterogeneity of primary oesophageal squamous carcinoma. 984 64

The incidence of adenocarcinoma of the distal esophagus is rapidly increasing in the Western world. The histopathological sequence of (Barrett's) metaplasia, which develops as a consequence of chronic reflux, to dysplasia and then to carcinoma is well established for these tumors. In Barrett's esophagus a variety of molecular changes have been characterized and correlated with tumor initiation and progression. Among the early changes in premalignant stages of metaplasia are alterations of the transcripts of FHIT, a presumptive tumor suppressor gene which spans the common fragile site FRA3B. Mutations of p53 seem to accumulate mainly in the transition from low to high grade dysplasia. Inactivation of other tumor suppressor genes by mutation (APC, p16) or hypermethylation (p16) as well as amplification of oncogenes such as cerbB2 are relatively late events in the development of adenocarcinoma. Among the phenotypic changes in Barrett's esophagus are an expansion of the Ki67 proliferation compartment which correlates with the degree of dysplasia. Moreover, accumulation of rab11 molecules which are involved in membrane trafficking has been reported to be specific for the loss of polarity seen in low grade dysplasia. Reduced expression of the cadherin/catenin complex as well as increased expression of various proteases develop chiefly in invasive carcinomas. Despite the progress that has been made in the identification of molecular markers in Barrett's carcinoma, to date the histopathological diagnosis of high grade dysplasia in endoscopic biopsies remains the best predictor of invasive cancer. Immunohistochemistry applying a panel of antibodies including p53, Mib-1 or rab11 can be helpful to diagnose regenerative metaplastic epithelium or low and high grade dysplasia.
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PMID:The molecular pathology of Barrett's esophagus. 1021 17

It is now accepted that altered E-cadherin-catenin complex expression in oesophageal cancer correlates with clinical and pathological parameters, while abnormal E-cadherin expression occurs early in Barrett's oesophagus. We evaluated immunohistochemically the expression and cellular localization of alpha-, beta-, and gamma-catenin, and E-cadherin in 5 dysplastic and 26 non-dysplastic cases of Barrett's oesophagus. Usually all three catenins were localized at the cell membrane, as was E-cadherin. A similar staining pattern for E-cadherin and the catenins was observed in all cases of non-dysplastic Barrett's syndrome. However, 60% (3/5) of cases with dysplasia showed loss of membranous beta-catenin staining and diffuse cytoplasmic distribution, with predominantly nuclear localization in two cases. Membranous staining and concomitant cytoplasmic localization of E-cadherin, alpha-catenin and gamma-catenin were seen in one case with abnormal beta-catenin immunoreactivity. Our results indicate that altered subcellular distribution of beta-catenin occurs frequently in dysplastic Barrett's oesophagus and possibly reflects the signalling function of this molecule.
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PMID:Abnormal expression of the E-cadherin-catenin complex in dysplastic Barrett's oesophagus. 1060 24

The incidence of both esophageal adenocarcinoma and Barrett's esophagus, a premalignant condition predisposing to this cancer, is rising rapidly. There is growing evidence that both of these conditions are related to the reflux of acid and bile into the esophagus. This results in inflammation and cell damage which initiates a sequence of events termed the metaplasia-dysplasia-carcinoma sequence in which the squamous epithelium is replaced by columnar epithelium exhibiting increasing degrees of dysplasia and overt malignancy. This sequence of events is underpinned by changes in cell cycling, such as accumulation of p16 and p53 mutations and increased cyclin D1 activity. Progression along this pathway is characterized by changes in intercellular adhesion, in particular, loss of adenomatous polyposis coli, reduced cadherin expression and increased catenin phosphorylation resulting in its nuclear translocation. Herein, we detail these molecular defects and propose how they may interrelate in an ordered progression in the development of esophageal adenocarcinoma.
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PMID:Barrett's esophagus: disregulation of cell cycling and intercellular adhesion in the metaplasia-dysplasia-carcinoma sequence. 1067 68

The recognition of key roles for cadherins in the determination of epithelial cell phenotype, migration, differentiation, and tumour dissemination have stimulated much interest in this family of adhesion molecules. In the gastrointestinal tract, alteration of the expression of classical cadherins with aberrant P-cadherin up-regulation, associated with co-expression or loss of E-cadherin expression, is seen in neoplastic transformation of oral and oesophageal squamous mucosa and in lesions representing early neoplastic transformation of glandular mucosa, such as aberrant crypt foci and metaplastic and adenomatous polyps. This same phenotype is seen in enterocytes adjacent to foci of ulceration in the intestine in colitis, including inflammatory bowel disease, and in colitis-associated dysplasia. In coeliac disease, reversible E-cadherin down-regulation correlates with the degree of villous atrophy, but in contrast with colitis, aberrant P-cadherin expression is not a feature. Aberrant epithelial P-cadherin expression is thus associated with a proliferative phenotype related to ulceration and neoplastic transformation in the gastrointestinal tract, which may confer a survival advantage on these cells, but the relative functional roles of P-cadherin and E-cadherin and the molecular mechanisms underlyingP-cadherin/catenin interactions have yet to be elucidated.
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PMID:Aberrant P-cadherin expression is a feature of clonal expansion in the gastrointestinal tract associated with repair and neoplasia. 1072 77

Animal models of colitis, which develop dysplasia and cancer similar to human ulcerative colitis are needed to further investigate the dysplasia cancer sequence. This study describes the expression of B-catenin and p53 along with the histopathology and inflammation scores as they relate to dysplasia and cancer in the dextran sulfate sodium (DSS) colitis model. Swiss Webster mice were fed with 5% DSS as follows: group A, four cycles of DSS, 84 days total (1 cycle = 7 days DSS + 14 days H(2)O); group B, four cycles DSS followed by 120 days H(2)O, 204 days total; group C, 7 days DSS followed by 180 days H(2)O, 187 days total; group D, 7 days DSS followed by 90 days H(2)O, 97 days total. The incidences of dysplasia and/or cancer were 15.8, 37.5, 18.1 and 0% in groups A-D, respectively. Dysplasia and/or cancer occurred as flat lesions or as dysplasia-associated lesion or mass (DALM) as observed in the human. Thirty-three percent of cancers had associated dysplasia. Within group A, inflammation scores were significantly higher in animals with dysplasia and/or cancer compared with those without dysplasia and/or cancer (P < 0. 05-P < 0.0001). Inflammation scores were significantly higher in animals with cancers versus those with dysplasia (P < 0.015) and in flat dysplasia and/or cancer versus DALM (P < 0.0042). B-catenin showed translocation from the cell membrane to the cytoplasm and/or nucleus in 100% of DALM and 5.8% of flat dysplasia and/or cancer. A total of 94.2% of flat dysplasia and/or cancer had exclusive cell membrane expression compared with 0% DALM (P < 0.0001). Only 7.4% of dysplasia and/or cancer showed nuclear expression of p53. In colitis-associated dysplasia and/or cancer in the DSS model: (i) histology resembles that in the human; (ii) inflammation plays a significant role in the dysplasia cancer sequence and whether dysplasia and/or cancer grows as a flat lesion or a DALM; (iii) the early molecular pathways are different for flat dysplasia and/or cancer versus DALM, with nuclear/cytoplasmic translocation of B-catenin as an early event in DALM but not flat dysplasia and/or cancer; and (iv) p53 has little or no role in dysplasia and/or cancer. This well characterized model provides an excellent vehicle for studying the roles of inflammation, the molecular events and the role of chemopreventive agents in colitis-associated neoplasia.
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PMID:Dysplasia and cancer in the dextran sulfate sodium mouse colitis model. Relevance to colitis-associated neoplasia in the human: a study of histopathology, B-catenin and p53 expression and the role of inflammation. 1075 13

Although dehydroepiandrosterone (DHEA) is recognized as one of the major adrenal androgens, its precise physiological role in the human endocrine system remains to be elucidated. In particular, the effect of DHEA on carcinogenesis has not been fully characterized. We undertook this study to determine whether DHEA has a chemopreventative effect on the precursors of colon cancer in a murine model of azoxymethane (AOM)-induced aberrant crypt foci (ACF). The number of ACF was significantly decreased in mice treated with 0.4% (p < 0.001) and 0.8% DHEA (p < 0.001), but there were no significant differences between DHEA-treated and control mice in terms of the ACF size, 3-catenin expression or level of dysplasia. This is the first study of colon cancer carcinogenesis demonstrating that DHEA treatment can decrease the number of ACF without apparently modifying their malignant potential. These data strongly suggest that DHEA might be a potential chemopreventative agent against human colon cancer.
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PMID:Chemoprevention of precursors to colon cancer by dehydroepiandrosterone (DHEA). 1226 89


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