Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1alpha,25-Dihydroxyvitamin D3 (1alpha,25(OH)2D3) has antitumor activity in addition to its classical action on calcium metabolism and bone tissue biology. It is thought to regulate the expression of multiple target genes and thus modulate processes critical for tumor growth and metastases. Here we show that 1alpha,25(OH)2D3 differentially regulates the expression of Id1 and Id2 genes, members of a family of transcriptional regulators of cell proliferation and differentiation. 1alpha,25(OH)2D3 induced epithelial differentiation in SW480-ADH human colon carcinoma cell line by promoting expression of the proteins implicated in adherent junction formation, including E-cadherin, and by inhibiting beta-catenin transcriptional activity. 1alpha,25(OH)2D3 activated the human Id1 gene promoter and rapidly induced Id1 RNA and protein. Ectopic overexpression of Id1 was not sufficient to induce E-cadherin, which was critical for the morphological changes induced by 1alpha,25(OH)2D3 in SW480-ADH cells. Conversely, Id2 transcription rate, RNA and protein levels were decreased by 1alpha,25(OH)2D3. Id2 downregulation by 1alpha,25(OH)2D3 mediated the antiproliferative effect of 1alpha,25(OH)2D3 on SW480-ADH cells. In addition, we showed that 1alpha,25(OH)2D3 changed the levels of the inducer of angiogenesis, vascular endothelial growth factor and the potent antiangiogenic factor thrombospondin-1, leading to a balanced change in the angiogenic potential of SW480-ADH human colon carcinoma cells.
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PMID:1alpha,25-Dihydroxyvitamin D3 regulates the expression of Id1 and Id2 genes and the angiogenic phenotype of human colon carcinoma cells. 1600 83

The potential correlation of E-cadherin reduction and Wnt2 up-regulation in determining the intracellular distribution of beta-catenin in gastric cancers was investigated by the methods of frozen tissue array-based immunohistochemistry, Western blot and RT-PCR analysis. It was revealed that membranous E-cadherin was reduced frequently in the two major subtypes of gastric cancer (intestinal gastric cancer, i-GC and diffuse gastric cancer, d-GC) and closely correlated with the risk of lymphoid node metastasis (P < 0.05). The reduction of membranous E-cadherin was paralleled with cytosolic and nuclear accumulation of beta-catenin and the increased Wnt2 expression. These results indicate that the reduced E-cadherin is a common genetic phenotype of GCs and plays beneficial roles in tumor metastasis. Altered beta-catenin distribution may result from the imbalance of E-cadherin production and Wnt expression, which confers on gastric cancer cells more aggressive behaviors.
Clin Exp Metastasis 2005
PMID:Frequent loss of membranous E-cadherin in gastric cancers: A cross-talk with Wnt in determining the fate of beta-catenin. 1613 82

In 140 mixed primary soft tissue sarcomas with a median follow-up of 6 years, the prognostic importance of tumor size, tumor depth, grade, necrosis, vascular invasion, and peripheral growth pattern (pushing versus infiltrating) was evaluated on whole-tumor sections. Immunohistochemical expression of Ki-67, p53, cyclin A, bcl-2, beta-catenin, CD44, and P-glycoprotein was determined using tissue microarray from the peripheral growth zone. Local recurrences developed in 17% of the patients and correlated with necrosis, vascular invasion, and cyclin A expression. No local recurrence developed in tumors with a pushing growth pattern, regardless of tumor grade and depth. Metastasis developed in 39% of the patients. Vascular invasion was identified in 36% of the tumors and was the strongest prognostic factor for metastasis with a hazard ratio of 3.5. Growth pattern and tumor necrosis were also strong prognostic factors for metastasis, whereas malignancy grade, tumor size, and tumor depth did not have any independent prognostic value. Immunostaining showed independent prognostic information for Ki-67, beta-catenin, CD44, and P-glycoprotein. The results indicate that whole-tumor sections could facilitate identification of vascular invasion, necrosis, and peripheral growth pattern and that immunohistochemical profiling from the growth zone also provides independent prognostic information for metastasis in soft tissue sarcoma.
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PMID:Improved prognostication in soft tissue sarcoma: independent information from vascular invasion, necrosis, growth pattern, and immunostaining using whole-tumor sections and tissue microarrays. 1615 63

Immunohistochemical analysis of the expression of E-cadherin, beta-catenin, and CD-44v6 proteins was carried out for evaluating the metastatic potential of colorectal cancer cells. Specific features of expression, distribution, and interactions of adhesive molecules in primary tumors of the large intestine and their metastases in the liver and lymph nodes were studied. Reduction and complete absence of E-cadherin expression were much more often observed in patients with colorectal cancer with metastases in the liver than in patients without metastases. Cytoplasmic immunoreactivity and nuclear translocation of beta-catenin were increased in more than 80% cases with colorectal adenocarcinoma with metastases. These changes in the expression of E-cadherin and beta-catenin in tumor cells can be regarded as factors of unfavorable prognosis of colorectal cancer. No significant relationship between expression of CD-44v6 protein and metastatic potential of cancer cells was detected.
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PMID:Expression of E-cadherin, beta-catenin, and CD-44v6 cell adhesion molecules in primary tumors and metastases of colorectal adenocarcinoma. 1622 88

EphB2, a receptor tyrosine kinase regulated by the beta-catenin/Tcf4 complex, is expressed in the proliferative compartment of mouse intestine and regulates bidirectional migration of intestinal precursor cells in the crypt-villus axis through repulsive interaction with Ephrin-B ligands. Recently, it has been shown that reduction of EphB activity accelerates colon tumour progression in the Apc(Min/+) mice. In this study, we examined the expression of EphB2 in normal colon, adenomas, primary colorectal cancers (CRCs), lymph node metastases and liver metastases using immunohistochemistry on tissue microarrays. In addition, EphB2 was overexpressed in SW480 colon cancer cells to study its effect in vitro. We found that EphB2 was expressed in 100% of normal colon crypt base cells, 78% of adenomas, 55.4% of primary CRCs, 37.8% of lymph node metastases and 32.9% of liver metastases (all differences were statistically significant at P < 0.001 compared with primary CRCs). Patients with CRCs that lose EphB2 expression had more advanced tumour stage (P = 0.005), poor differentiation (P < 0.001), poor overall survival (P = 0.005) and disease-free survival (P = 0.001), with the latter being independent of tumour stage. In vitro studies showed that overexpression of EphB2 inhibited colon cancer cell growth in colony formation assay and activation of EphB2 receptor inhibited colon cancer cell adhesion and migration. Our data demonstrated a progressive loss of EphB2 expression in each critical step of colon carcinogenesis, including the onset of invasion, dedifferentiation and metastasis which are paralleled by adverse patient outcome. EphB2 may achieve its tumour suppressor function through regulation of cell survival, adhesion and migration.
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PMID:Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumours. 1627 70

Integrin-linked kinase (ILK) has been implicated in the development and progression of several human malignancies. However, the role of ILK in human colon cancer progression is not well established, neither have its possible in vivo downstream effectors in the disease been identified. We studied, by immunohistochemistry, ILK, beta-catenin, E-cadherin, p-Akt and p-FKHR protein expression in 125 primary colon carcinomas and 45 corresponding lymph node metastases. ILK was expressed in 98.4% of the primary tumours and in 100% of metastatic lesions. The levels of ILK expression correlated strongly with tumour invasion, tumour grade and stage and were significantly higher in metastatic tumours. Activation of beta-catenin, down-regulation of E-cadherin and activation of the Akt-FKHR pathway correlated significantly with both ILK expression and tumour progression parameters. In conclusion, our results suggest that ILK may have an important role in progression of human colon cancer, possibly through in vivo regulation of beta-catenin, E-cadherin and Akt pathways. Our study also provides some evidence implicating p-FKHR in human colon carcinogenesis and ILK signalling.
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PMID:ILK over-expression in human colon cancer progression correlates with activation of beta-catenin, down-regulation of E-cadherin and activation of the Akt-FKHR pathway. 1627 19

Features of expression, distribution and interaction of E-cadherin, beta-catenin and CD-44v6 were immunologically assayed in samples from primary colorectal tumors (129) and their metastases to the lymph nodes (35) and liver (92). Reduction or total absence of E-cadherin expression was significantly more typical of tumors metastasizing, at different stages, to the liver (64/84, 76%) than in metastasis-free ones (14/45, 31%) (p=0.014). Enhanced cytoplasmic immunoreactivity and beta-catenin nuclear translocation occurred in 80% of disseminated tumors. Such alterations of E-cadherin, beta-catenin expression may be regarded as unfavorable prognosis factors involved in colorectal cancer. No significant correlation between CD-44v6 expression and tumor cell ability to metastasize was recorded.
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PMID:[The features of expression of cellular adhesion molecules in primary colorectal cancer and its metastases]. 1627 97

Interaction of nuclear beta-catenin and TCF4 is the end point of canonical Wnt signaling, which is believed to trigger the transcription of multiple cancer-associated genes, including CD44. So far, the combined status of beta-catenin and TCF4 and its relevance for lymph node metastasis and CD44 expression have not been well studied in gastric cancers (GCs). To address these issues, we examined 31 GCs, 17 premalignant tissues, 10 noncancerous gastric mucosae, 17 regional lymph node metastases, and 4 human GC cell lines (MGC803, MGC823, AGS, and HGC-27) using immunohistochemical and immunofluorescence staining, reverse transcriptase polymerase chain reaction, and Western blot analysis. Frequent TCF4 up-regulation and nuclear translocation of beta-catenin were found in both primary and metastatic tumors. Standard CD44 was detected in all gastric tissue samples. The frequency of variant CD44 expression increased in parallel with stepwise gastrocarcinogenesis and tumor spread, but the rates of detection did not match that of nuclear beta-catenin and TCF4, especially in the premalignant and noncancerous samples. The data from the 4 cell lines were in accordance with the in vivo findings in terms of beta-catenin nuclear translocation, TCF4 activation, and CD44 expression. Our results suggest an established Wnt signaling pathway in most GCs, a close correlation of beta-catenin/TCF4-mediated signaling with tumor dissemination, and the unlikelihood of a direct effect of activated Wnt signaling on CD44 expression. The influence of beta-catenin-TCF4 interaction on alternative CD44 splicing was not established. These 3 alterations may be regarded as unfavorable features of GC.
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PMID:Nuclear translocations of beta-catenin and TCF4 in gastric cancers correlate with lymph node metastasis but probably not with CD44 expression. 1631 Nov 23

129 primary colon carcinomas, 35 metastases to the lymph nodes and 92 metastases to the liver are studied. Reduction or complete absence of E-cadherin was more frequently observed in cases with liver metastases (64/ 84 - 76%) than in patients without metastases (14/45 - 31%) (p = 0,014). Also, beta-catenin expression was more frequent in cases with metastases. These results of E-cadherin and beta-caterin expression, changes may be considered as factors of unfavourable prognosis. No links between CD44v6 expression and metastases was found.
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PMID:[Immunohistochemical study of E-cadherin, beta-catenin and CD-44v6 expression in the cells of primary colon cancer and its metastases]. 1640 20

The histological features that accompany the development and progression of solid tumors are known to be controlled by a distinct cascade of molecular events. One such event is the inactivation of tumor suppressor genes, such as the adenomatous polyposis coli (APC) gene. Disruption of the cadherin-catenin cell adhesion complex also plays a role in the initial steps of cancer invasion and metastasis whereas alterations in cell structural molecules, such as tubulin, may contribute to the cancer phenotype. The understanding of the status of these molecules in ESSC may provide novel markers that could impact on management of the disease. The present study examined alterations in the microsatellite sequence of the APC gene via fluorescent-based polymerase chain reaction in 100 cases of primary esophageal squamous cell carcinoma. In addition, the expression of E-cadherin, alpha- and beta-catenin, and alpha- and beta-tubulin was analyzed using immunohistochemistry. These data were then statistically compared with each other as well as the relevant clinicopathologic data. Although the APC markers (D5S210, D5S346, D5S299, and D5S82) tested did show an overall high frequency of allelic imbalance/loss of heterozygosity (62.48%) and microsatellite instability (41.27%), they did not show prognostic significance in the study cohort and were not correlated with the immunohistochemical data. The tubulin proteins showed no significant change in expression in the tumor tissue The decreased immunoreactivity of E-cadherin was statistically correlated with the presence of lymph node metastases (P = .0180). Although alpha- and beta-catenin as well as E-cadherin showed no direct prognostic value, E-cadherin may warrant further investigation as an indirect prognostic indicator by allowing more accurate prediction of lymph node metastases.
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PMID:Microsatellite analysis of the APC gene and immunoexpression of E-cadherin, catenin, and tubulin in esophageal squamous cell carcinoma. 1642 11


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