Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of genetic changes have been documented in prostate cancer, ranging from allelic loss to point mutations and changes in DNA methylation patterns (summarized in Fig. 1). To date, the most consistent changes are those of allelic loss events, with the majority of tumors examined showing loss of alleles from at least one chromosomal arm. The short arm of chromosome 8, followed by the long arm of chromosome 16, appear to be the most frequent regions of loss, suggesting the presence of novel tumor suppressor genes. Deletions of one copy of the Rb and p53 genes are less frequent, as are mutations of the p53 gene, and accumulating evidence suggests the presence of an additional tumor suppressor gene on chromosome 17p, which is frequently inactivated in prostate cancer. Alterations in the E-cadherin/alpha-catenin-mediated cell-cell adhesion mechanism appear to be present in almost half of all prostate cancers and may be critical to the acquisition of metastatic potential of aggressive prostate cancers. Finally, altered DNA methylation patterns have been found in the majority of prostate cancers examined, suggesting widespread alterations in methylation-modulated gene expression. The presence of multiple changes in these tumors is consistent with the multistep nature of the transformation process. Finally, efforts to identify prostate cancer susceptibility loci are under way and may elucidate critical early events in prostatic carcinogenesis.
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PMID:Genetic alterations in prostate cancer. 758 26

The aim of this study was to evaluate the expression of E-cadherin as a potential marker for the prognosis of thyroid carcinomas. In normal thyroid (n = 8), the expression of E-cadherin messenger ribonucleic acid levels was uniformly high and seemed to be restricted to thyrocytes. Steady-state messenger ribonucleic acid levels and immunostaining were both completely lost in undifferentiated thyroid carcinomas (n = 7) and were variably reduced in differentiated thyroid carcinomas (n = 44). In a follow-up study during a mean of 4.5 +/- 1.4 yr, E-cadherin messenger ribonucleic acid and immunohistochemical expression were compared with the initial clinicopathological parameters and with locoregional recurrence and the development of nodal or distant metastases in differentiated thyroid carcinomas. Immunohistochemical expression of E-cadherin was greatly reduced with the progression to primary tumor stage 4 (pT4) tumors. In parallel, patients with pT4 tumors had a higher rate of locoregional tumor recurrence and distant metastasis than did the group of patients with pT1-3 tumors. In 5 of 29 patients with pT4 tumors, positive E-cadherin staining of more than 30% of the cells was detected. None of these patients showed signs of a regional recurrence or distant metastases during an observation period of 4.3 +/- 1.1 yr. In 13 patients with E-cadherin-positive tumors, none developed new distant metastases which was in contrast to 7 of the group of 31 patients with less than 30% E-cadherin-positive cells. Thus, E-cadherin expression seems to be associated with the dedifferentiation, progression, and metastatic spread of thyroid carcinomas and may be a useful marker for the prognosis of these tumors.
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PMID:Clinical significance of E-cadherin as a prognostic marker in thyroid carcinomas. 760 73

There is convincing evidence that a reduced expression of the E-cadherin cell-cell adhesion molecule associates with low tumor grade and poor prognosis in prostate cancer patients. However, little is known on how E-cadherin levels are regulated in human prostate cancer cells. We have inspected the effect of both androgens and estrogen on the expression of E-cadherin in the hormone-responsive LNCaP prostate tumor cell line, which is endowed with both androgen and estrogen receptors. Using both Dot Blot analysis and immunocytochemistry we have observed that either steroid significantly increased E-cadherin levels in these cells; this effect was not reversed by the simultaneous addition of the relevant antagonist, hydroxyflutamide or ICI-182,780.
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PMID:Sex steroids up-regulate E-cadherin expression in hormone-responsive LNCaP human prostate cancer cells. 762 77

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

The immunostaining (ABC method) of E-cadherin and alpha-catenin were performed on 46 esophageal cancers, 67 gastric cancers, 100 colon cancers. E-cadherin and alpha-catenin expression was evaluated as preserved and reduced according to the proportion of positive cells, respectively. The reduction of alpha-catenin expression was more significantly related to lymph node metastasis than that of E-cadherin. Furthermore, the frequency of hematogenous liver metastasis in preserved E-cadherin expression and reduced alpha-catenin expression was significantly higher than that in another combination of E-cadherin and alpha-catenin expression, in gastric and colon cancer. The reduction of alpha-catenin expression was associated with declined intercellular adhesiveness, which occasionally was not accompanied by reduction of E-cadherin. Therefore, the expression of alpha-catenin might more sensitively indicated cell-cell adhesion, predicting tumor metastasis.
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PMID:[Correlation between the intercellular adhesion molecule (E-cadherin) and its associated protein (alpha-catenin) expression and metastasis in human digestive cancers]. 762 95

We examined expression of E-cadherin cell-cell adhesion molecule, which is supposed to have invasion-suppressing activity, in 53 cases with endometrial carcinoma. Fresh frozen sections were immunostained with a mouse monoclonal antibody to human E-cadherin (HECD-1). E-cadherin expression was inversely correlated with grade of tumor (p = 0.0267), depth of myometrial invasion (p = 0.0146) and pelvic and paraaortic node metastases (p = 0.0184 and p = 0.0419, respectively). Multivariate analysis revealed that among histologic grade, nuclear grade, and E-cadherin expression, E-cadherin expression was most strongly correlated with depth of myometrial invasion (p = 0.0491). These results suggest that decreased expression of E-cadherin facilitates invasion of endometrial carcinoma.
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PMID:[Abnormal E-cadherin expression as a risk factor for deep myometrial invasion and lymph node metastasis in endometrial carcinoma]. 762 96

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

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

Tumour cell motility and attachment are crucial requirements in the formation of metastatic lesions. These properties are affected by a number of cytokines including hepatocyte growth factor/scatter factor (HGF/SF) and several immunoregulatory proteins, including interleukin-12 (IL-12). Although IL-12 has been reported to exhibit potent anti-tumour effects in vivo, a direct effect of IL-12 on cancer cells has not been reported. We show here that IL-12 directly inhibited the attachment of the human colon cancer cell lines HRT18, HT29 and HT115 to Matrigel, HGF/SF-stimulated cell motility and HGF/SF-induced cell invasion through a reconstituted basement membrane. IL-12 did not affect the growth of these cell lines. Flow cytometry, Western analysis and immunohistochemistry revealed an up-regulation of E-cadherin cell-surface adhesion molecules. These direct effects of IL-12 on colon cancer cells suggest a potentially important role for IL-12 in metastasis.
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PMID:Inhibition of cancer cell motility and invasion by interleukin-12. 764 24

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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