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)

The Armadillo protein p120(ctn) associates with the cytoplasmic domain of cadherins and accumulates at cell-cell junctions. Particular Armadillo proteins such as beta-catenin and plakophilins show a partly nuclear location, suggesting gene-regulatory activities. For different human E-cadherin-negative carcinoma cancer cell lines we found expression of endogenous p120(ctn) in the nucleus. Expression of E-cadherin directed p120(ctn) out of the nucleus. Previously, we reported that the human p120(ctn) gene might encode up to 32 protein isoforms as products of alternative splicing. Overexpression of p120(ctn) isoforms B in various cell lines resulted in cytoplasmic immunopositivity but never in nuclear staining. In contrast, upon expression of p120(ctn) cDNAs lacking exon B, the isoforms were detectable within both nuclei and cytoplasm. A putative nuclear export signal (NES) with a characteristic leucine-rich motif is encoded by exon B. This sequence element was shown to be required for nuclear export and to function autonomously when fused to a carrier protein and microinjected into cell nuclei. Moreover, the NES function of endogenously or exogenously expressed p120(ctn) isoforms B was sensitive to the nuclear export inhibitor leptomycin B. Expression of exogenous E-cadherin down-regulated nuclear p120(ctn) whereas activation of protein kinase C increased the level of nuclear p120(ctn). These results reveal molecular mechanisms controlling the subcellular distribution of p120(ctn).
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PMID:Nuclear localization of the p120(ctn) Armadillo-like catenin is counteracted by a nuclear export signal and by E-cadherin expression. 1039 33

Dysfunction of the cadherin-catenin complex, a key component of adherens junctions, is thought to confer invasive potential to cells. The aim of this study is to examine the expression and function of the E-cadherin/catenin complex in gastric carcinoma cell lines. Expression of E-cadherin, alpha, beta and gamma-catenin and p120ctn, and of the adenomatous polyposis coli protein (APC), together with function of the cadherin-catenin complex was examined in a panel of gastric carcinoma cell lines, using immunocytochemistry, Western blotting and a cell-cell aggregation assay. Protein interactions were examined by sequential immunoprecipitation and immunoblotting with antibodies to E-cadherin, alpha, beta and gamma-catenin, p120ctn and APC. Abnormalities of E-cadherin, alpha- and beta-catenin expression, were associated with disturbance of E-cadherin-catenin complex composition, loss of membranous localization and loss of calcium-dependent aggregation in six gastric carcinoma cell lines. APC protein expression and interaction with beta-catenin was preserved in five cell lines. We demonstrate frequent abnormalities of expression and function of E-cadherin and catenins, and associated disturbance of E-cadherin-mediated intercellular adhesion in gastric carcinoma cell lines. These findings support the tumour suppressor role of the E-cadherin and its contribution to the development and progression of the neoplastic phenotype in gastric carcinoma.
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PMID:Abnormal expression and function of the E-cadherin-catenin complex in gastric carcinoma cell lines. 1040 33

Familial cancers associated with genetic background are of the most intensively investigated diseases in recent years. The phenotype is apparent with most of these diseases and can easily be traced through family history. Induction in familial cancer appears, on current evidence, to be not different from that observed in sporadic cancer. The first suppressor gene Rb gene was cloned from retinoblastoma. There are two representative hereditary colorectal cancers: familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC). The gene responsible for FAP (APC gene) was cloned in 1991. The APC gene is a negative regulator of beta-catenin and is considered to play the role of gatekeeper in the adenoma carcinoma sequence. Thereafter a group of genes, human homologues of mismatch repair genes (hMSH2, hMLH1, hPMS1, hPMS2, hMSH6), have been identified as the genes responsible for HNPCC. These are called care taker genes, which serve to maintain genetic stability. Therefore, if one of those genes undergoes mutation, the rate of mutation increases significantly. It has only been in the last 20 years that familial cancer has become an important issue. In association with such advances, predictive testing can now be performed on at risk persons. Persons at risk can thus be accurately counseled and screened for early detection of disease.
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PMID:[Familial cancer: recent advances]. 1041 Jan 40

This study examined the relationship between the expression of E-cadherin or beta-catenin in murine adenocarcinomas and their hematogenous metastatic propensity, assessed by both spontaneous and artificial lung metastasis. Seven different carcinomas, syngeneic to C3Hf/Kam mice were used: 4 mammary carcinomas (MCa-4, MCa-29, MCa-35, and MCa-K), ovarian carcinoma OCa-I, hepatocarcinoma HCa-I, and adenosquamous carcinoma ACa-SG. These tumors vary widely in their ability to spontaneously metastasize to the lung (from 0 to 100% metastatic incidence), and their cells greatly differ in their ability to form artificial lung nodules when injected i.v. Primary tumors in the leg were assessed for E-cadherin and beta-catenin expression by western blotting. The expression of both proteins showed wide variation among the tumors; however, the expression of E-cadherin correlated well with that of beta-catenin. There was significant inverse correlation between the expression of E-cadherin, as well as beta-catenin, and the incidence of both spontaneous and artificial lung metastases from these tumors. Spontaneous metastases of highly metastatic HCa-I and moderately metastatic MCa-35 were significantly lower in E-cadherin and beta-catenin expression than their corresponding primary tumors were. Thus, the propensity of murine carcinomas for hematogenous spread is highly related to E-cadherin and beta-catenin levels in primary tumors. The inverse correlation between the expression of these molecules and spontaneous and artificial metastases implies that tumor cells with low E-cadherin and beta-catenin content have increased ability to enter the vascular circulation at the primary tumor site and to colonize distant tissues.
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PMID:Low E-cadherin and beta-catenin expression correlates with increased spontaneous and artificial lung metastases of murine carcinomas. 1041 Nov 10

We discovered a unique feature of a subclone of the pancreatic carcinoma cell line A818. A818-1-derived hollow-spheres developed under three-dimensional growth conditions. Hollow-spheres consist of a single layer of 50-200 epithelial cells surrounding an inner lumen. In contrast to A818-1, the subclone A818-4 and all other pancreatic tumor cell lines tested (n = 5), formed spheroids as the only three-dimensional phenotype. A dramatically reduced proliferation rate compared to the corresponding monolayer was observed in hollow-spheres when bromodeoxyuridine (BrdU) incorporation was measured. This finding was confirmed by immunostaining using the MIB-1 antibody. Mechanically disrupted hollow-spheres not only attached but also grew as monolayer with the same doubling time as the founder cells. Hollow-spheres developed in fetal calf serum (FCS) containing RPMI 1640 medium without additionally added cytokines. A818-1 hollow-sphere formation and integrity was influenced by interferon-gamma. Tumor necrosis factor-alpha (TNF-alpha) led to cell death. Exogenously added hepatocyte growth factor (HGF) showed no effect neither on hollow-sphere formation nor on the integrity of completely developed hollow-spheres. Moreover, no changes were observed when cells were treated with a neutralizing antibody for HGF. Interestingly, hollow-spheres showed intensive immunoreactivity for the HGF-receptor (c-met) and its ligand (HGF). Immunostaining for the biliary glycoprotein (BGP), the non-specific cross-reacting antigen 95 (NCA95) and beta-catenin revealed a polar organization of hollow-spheres. Immunhistochemically, hollow-spheres were negative for the carcinoembryonic antigen (CEA). When hollow-spheres were embedded into matrigel, duct-like tubes grew out. Taken together, A818-1 hollow-spheres resemble normally differentiated duct-like structures and will serve as an excellent model to study differentiation of human pancreatic epithelial cells.
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PMID:Hollow-spheres: a new model for analyses of differentiation of pancreatic duct epithelial cells. 1041 53

The E-cadherin/catenin complex plays an essential role in maintaining intimate intercellular associations and is considered to be involved in tumor metastasis and suppressing invasion by cancer cells. We have analyzed the expression of E-cadherin/catenin complex in a series of nasopharyngeal carcinoma (NPC) specimens using immunohistochemistry and immunoblotting. Data are correlated with the patients' clinicopathological parameters, including the clinical stage, presence of intracranial invasion, presence of lymph node or distant metastasis, and histological grading. The E-cadherin/catenin complex is down-expressed in most of the samples examined. Correlation with clinicopathological parameters shows that expression of alpha- and beta-catenin is associated with the occurrence of intracranial invasion.
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PMID:Expression of E-cadherin/catenin complex in nasopharyngeal carcinoma: correlation with clinicopathological parameters. 1042 4

The immunohistochemical expression pattern of beta-catenin has been correlated with beta-catenin gene mutations, clinicopathological features, and disease outcome in 69 stage I and II ovarian carcinomas. beta-Catenin expression was localized in the nuclei, in addition to the cytoplasm and membrane, in 11 tumors (16%): nine endometrioid carcinomas with widespread nuclear expression and two serous carcinomas with focal nuclear expression. The remaining 58 carcinomas (84%) only had membranous beta-catenin expression. All but one of the endometrioid carcinomas with nuclear beta-catenin expression had considerable squamous metaplasia, and five of these cases had large areas of endometrioid tumor of low malignant potential. In addition, beta-catenin nuclear expression was observed in atypical epithelial cells in endometriotic glands adjacent to an endometrioid carcinoma. Sequencing was performed on 25 tumors and corresponding normal tissue: all 13 endometrioid tumors as well as 12 carcinomas of other histological types (four serous, two clear cell, two mucinous, and two mixed). There were oncogenic mutations in the phosphorylation sequence for GSK-3beta in exon 3 of the beta-catenin gene in seven endometrioid carcinomas with beta-catenin nuclear expression. Three mutations affected codon 32 (D32G, D32Y, and D32Y), one affected codon 33 (S33C), two affected codon 37 (S37C and S37F), and one affected codon 41 (T41A). No mutations were observed in the other 18 carcinomas analyzed, comprising two endometrioid and two serous carcinomas with beta-catenin nuclear expression, and 14 carcinomas of different histological types with only membranous expression. In the univariate and multivariate survival analyses, beta-catenin nuclear expression was selected as an indicator of good prognosis, because no patient whose tumor expressed beta-catenin in the nuclei showed relapses or died, in contrast to the 19 relapses and deaths among patients with tumors that only had beta-catenin membranous expression, including three of the four patients with endometrioid carcinomas. Oncogenic beta-catenin mutation is characteristic of a group of endometrioid carcinomas with a good prognosis, most of which originate from previous benign or borderline lesions. Endometrioid carcinomas with exclusively membranous expression of beta-catenin seem to represent a different subgroup of carcinomas that probably have a worse prognosis. In early-stage ovarian cancer, determination of the beta-catenin expression pattern could prove to be a useful marker for selecting low-risk patients.
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PMID:beta-catenin expression pattern in stage I and II ovarian carcinomas : relationship with beta-catenin gene mutations, clinicopathological features, and clinical outcome. 1043 45

Defects in the APC-beta-catenin pathway are common in colon cancer. We investigated whether aberrant regulation of upstream ligands stimulating this pathway occur in colon cancer. Using RNAase protection analysis, six out of eight wnt genes were expressed in 14 matched cases of normal, adenomatous and malignant colorectal tissues. Wnt 2 and wnt 5a were significantly up-regulated in the progression from normal through adenoma to carcinoma. Transcripts for wnts 4, 7b, 10b and 13, but not wnt 2 and wnt 5a were detected in several colorectal cell lines. In situ hybridization demonstrated that wnt 2 and wnt 5a transcripts were mainly in the lamina propria/stroma region with labelling predominantly in macrophages. Immunostaining with CD68 confirmed the wnt-expressing cells as macrophages. These results show a major difference in wnt expression in colon cancer compared to colon adenomas and suggest stromal wnt expression may play a role in tumour progression.
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PMID:Up-regulation of macrophage wnt gene expression in adenoma-carcinoma progression of human colorectal cancer. 1050 76

Previous studies have reported predominantly nuclear localization of beta-catenin as a role for colorectal carcinogenesis. In this study, we examined the immunohistochemical expression of beta-catenin and p53 protein in 90 colonic neoplasms {33 carcinomas in adenoma (CIA), 28 high grade adenomas and 29 low grade adenomas}, resected by colonic endoscopy. Out of 33 CIAs. 28 (84.8%) cases showed predominantly nuclear localization of beta-catenin, and that was significantly higher than those of both high grade (46.4%) and low grade (13.8%) adenomas. The positiveness of p53 expression in CIAs was 51.5% (17/33), while 17.9% in high grade and 3.4% in low grade adenomas. However, there was no correlation between both protein expressions (p = 0.3472, chi 2 test). The results suggests that nuclear localization and accumulation of beta-catenin is earlier event than that of p53 mutation in adenoma-carcinoma sequence, and is useful as a marker in histopathological diagnosis for malignant conversion as well as p53.
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PMID:[The relationship between the histopathological atypia and expression of beta-catenin in colonic neoplasms resected by endoscopy; comparison with that of p53 protein]. 1051 18

The role of cadherins and catenins in the progression of thyroid carcinoma is unclear. We have investigated alpha-, beta- and gamma-catenins and p120(ctn) in relation to the expression of cadherins in human anaplastic thyroid-carcinoma cell lines (HTh7, HTh74, C643 and SW1736) with Western blotting and immunofluorescence. E-cadherin was lacking except in SW1736, which consisted of E-cadherin-positive (approx. 5%) and -negative cells. The alpha- and beta-catenin levels were similar to those of primary cultured non-neoplastic (E-cadherin-positive) human thyrocytes. In contrast, the expression of gamma-catenin was low and variable, correlating with the different levels of cytokeratin in the same cells (HTh74 > SW1736 > C643 > HTh7). p120(ctn) resolved as a doublet in Western blots; the approximately 100-kDa band also found in non-neoplastic epithelial cells was reduced whereas the approximately 115-kDa band, corresponding to the fibroblast-type isoform of p120(ctn), was neo-expressed. A DNA-demethylating agent, 5-aza-2'-deoxycytidine, up-regulated E-cadherin in SW1736 and gamma-catenin in SW1736 and C643, whereas the other cell lines were unresponsive; other catenins were not affected. The catenins were generally distributed along the cell borders. Immunostaining, cell-surface biotinylation and co-immunoprecipitation revealed that all cell lines expressed N-cadherin in connection with beta-catenin at the plasma membrane. Incubation with an N-cadherin antibody disrupted cell-cell adhesion. We conclude that E-cadherin-negative anaplastic thyroid-carcinoma cell lines display functional N-cadherin/beta-catenin complexes, partial or complete loss of gamma-catenin, and isoform shift of p120(ctn). The unequal expression of E-cadherin and gamma-catenin and the variable response to DNA de-methylation suggest that anaplastic thyroid carcinoma is not a uniform entity.
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PMID:N-cadherin-mediated adhesion and aberrant catenin expression in anaplastic thyroid-carcinoma cell lines. 1052 9


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