Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Loss of E-cadherin-mediated cell-cell adhesion and expression of proteolytic enzymes characterize the transition from benign lesions to invasive, metastatic tumor, a rate-limiting step in the progression from adenoma to carcinoma in vivo. A soluble E-cadherin fragment found recently in the serum and urine of cancer patients has been shown to disrupt cell-cell adhesion and to drive cell invasion in a dominant-interfering manner. Physical disruption of cell-cell adhesion can be mimicked by the function-blocking antibody Decma. We have shown previously in MCF7 and T47D cells that urokinase-type plasminogen activator (uPA) activity is up-regulated upon disruption of E-cadherin-dependent cell-cell adhesion. We explored the underlying molecular mechanisms and found that blockage of E-cadherin by Decma elicits a signaling pathway downstream of E-cadherin that leads to Src-dependent Shc and extracellular regulated kinase (Erk) activation and results in uPAgene activation. siRNA-mediated knockdown of endogenous Src-homology collagen protein (Shc) and subsequent expression of single Shc isoforms revealed that p46(Shc) and p52(Shc) but not p66(Shc) were able to mediate Erk activation. A parallel pathway involving PI3K contributed partially to Decma-induced Erk activation. This report describes that disruption of E-cadherin-dependent cell-cell adhesion induces intracellular signaling with the potential to enhance tumorigenesis and, thus, offers new insights into the pathophysiological mechanisms of tumor development.
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PMID:Induction of uPA gene expression by the blockage of E-cadherin via Src- and Shc-dependent Erk signaling. 1722 83

The mechanism that drives the growth of some colonic adenomas towards malignancy, while permitting others to remain for decades in quiescence, remains unknown. Diets can alter the growth rate of intestinal tumours but it is still unknown whether diets are able to alter the molecular biology of these adenomas in a way that predicts further outcome. To address this issue we fed Min/+ mice with two diets known to lead to different adenoma outcomes: a high-fat control diet (n 15) or a high-fat inulin-enriched (10 % w/w) diet (n 13). To study the effect of diet on cell signalling during adenoma growth, the adenomas of each Min/+ mouse were divided into three size-categories, and the levels of beta-catenin, E-cadherin, cyclin D1 and matrix metalloproteinase-9, which are known to be involved in colon tumorigenesis, were determined. The growth-promoting inulin diet resulted in more large adenomas than the control feeding (P = 0.003) and doubled the total area of the adenomas (P = 0.008). The inulin diet increased the expression of nuclear beta-catenin (P = 0.004) and its target cyclin D1 (P = 0.017) as the adenomas increased in size from small to large, indicating the presence of an accelerated cancerous process. Neither phenomenon was seen in the control group during adenoma growth. Our results suggest that in addition to the number, size, and growth rate of adenomatous polyps, the signalling pattern of the adenomas should also be considered when evaluating preventive dietary strategies.
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PMID:Inulin results in increased levels of beta-catenin and cyclin D1 as the adenomas increase in size from small to large in the Min/+ mouse. 1797 70

The epithelial-mesenchymal transition (EMT) occurs commonly during carcinoma invasion and metastasis, but not during early tumorigenesis. Microarray data demonstrated elevation of vimentin, a mesenchymal marker, in intestinal adenomas from Apc Min/+ (Min) mice. We have tested the involvement of EMT in early tumorigenesis in mammalian intestines by following EMT-associated markers. Elevated vimentin RNA expression and protein production were detected within neoplastic cells in murine intestinal adenomas. Similarly, vimentin protein was detected in both adenomas and invasive adenocarcinomas of the human colon, but not in the normal colonic epithelium or in hyperplastic polyps. Expression of E-cadherin varied inversely with vimentin. In addition, the expression of fibronectin was elevated while that of E-cadherin decreased. Canonical E-cadherin suppressors, such as Snail, were not elevated in the same tumor. Elevated vimentin expression in the adenoma was not correlated with persistent Ras signaling, but was strongly correlated with reduced proliferation indices, active Wnt signaling, and TGF-beta signaling, as demonstrated by its dependence on Smad3. We designate our observations of expression of only some of the canonical features of EMT as "truncated EMT". These unexpected observations are interpreted as reflecting the involvement of a core of the EMT system during the tissue remodeling of early tumorigenesis.
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PMID:Intestinal adenomagenesis involves core molecular signatures of the epithelial-mesenchymal transition. 1832 51

Pituitary adenomas producing almost exclusively growth hormones (GH) have been ultrastructurally classified into two distinct types: densely granulated somatotroph (DG) adenomas and sparsely granulated (SG) adenomas. Fibrous body (FB), an intracytoplasmic globular aggregation of cytokeratin (CK) filaments, is a hallmark of SG adenomas. Under light microscope, FB could be identified by CK immunohistochemistry as a dot-pattern immunoreaction versus a perinuclear pattern for cells without FB. However, it has been noted that numerous adenomas contain mixed populations of the two patterns. To clarify clinicopathological characteristics of the adenomas with mixed populations ("intermediate type" adenomas) and to confirm clinicopathological differences between strictly defined DG-type and SG-type adenomas, we performed this study on 104 GH cell adenomas. Having segregated "intermediate-type" adenomas (26 cases), we found significant differences between typical DG-type (47 cases) and SG-type adenomas (31 cases); SG-type adenomas had younger ages (44 vs. 50), higher frequency of macroadenomas (86% vs. 58%), invasiveness (65% vs. 38%), advanced grades (3 or 4) in Knosp's classification (50% vs. 24%), and weaker immunoreaction for GH, beta-TSH, alpha-subunit, E-cadherin, and beta-catenin. Clinicopathological characteristics of "intermediate-type" adenomas were identical to those of DG-type adenomas. These findings confirm that SG-type adenoma is a distinct section of GH cell adenomas with special properties and biological behavior, and suggest that intermediate-phenotype adenomas are enrolled in DG-type adenomas. Special properties and biological behavior of SG-type adenomas may appear after the majority of tumor cells possess a fully developed fibrous body.
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PMID:Clinicopathological features of growth hormone-producing pituitary adenomas: difference among various types defined by cytokeratin distribution pattern including a transitional form. 1862 56

The pathogenesis of duodenal adenomas is not well elucidated. Much of the literature pertains to ampullary adenomas and those associated with familial adenomatous polyposis (FAP). In this study, we evaluated the molecular features of a series of sporadic duodenal adenomas (n=22) that developed distal to the ampulla, and compared them with the features of sporadic ampullary adenomas (n=9) and FAP-related polyps (n=12). Using a combination of immunohistochemical studies [cytokeratins 7 and 20, E-cadherin, beta-catenin, p53, MLH-1, MSH-2, MSH-6, and O6-methylguanine methyltransferase (MGMT)], DNA sequencing [beta-catenin, adenomatous polyposis coli (APC), p53, KRAS, and BRAF], and a polymerase chain reaction-based microsatellite instability assay; we assessed each case for abnormalities in the Wnt signaling and mitogen-activated protein kinase pathways and DNA repair mechanisms. Wnt signaling pathway abnormalities occurred in sporadic, nonampullary (82%), and ampullary (77%) adenomas at comparable rates, usually reflecting nuclear beta-catenin immunostaining (64% and 44%, respectively), and APC rather than beta-catenin, mutations. KRAS mutations were infrequent in sporadic, nonampullary adenomas (18%), and FAP-related adenomas (9%); moderately frequent in ampullary adenomas (44%); and none of the cases harbored BRAF mutations. Only 4 (13%) sporadic adenomas showed nuclear p53 staining, but no p53 mutations were detected in exons 5 to 8. Loss of O-methylguanine methyltransferase immunostaining was identified in 1 sporadic, nonampullary adenoma, and none of the polyps in any group showed loss of MLH-1, MSH-2, or MSH-6 staining, or high-frequency microsatellite instability. We conclude that sporadic and FAP-related adenomas show similar molecular features, regardless of their anatomic location. Similar to colorectal adenomas, they harbor APC and KRAS mutations; but BRAF mutations, p53 alterations, and DNA mismatch repair abnormalities are rare.
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PMID:Immunohistochemical and molecular features of sporadic and FAP-associated duodenal adenomas of the ampullary and nonampullary mucosa. 1867 Mar 49

The aim of the present study was to assess any variation in the immunohistochemical expression of E-cadherin in benign and malignant salivary gland tumors. A total of 60 cases of benign and malignant salivary gland tumors were evaluated immunohistochemically for E-cadherin expression. These included 10 cases of pleomorphic adenoma (PA), 2 cases of canalicular adenoma (CA), 2 cases of myoepithelioma (MY), 24 cases of adenoid cystic carcinoma (ACC), 12 cases of mucoepidermoid carcinoma (MEC), 9 cases of adenocarcinoma (AC) and 1 case of carcinoma ex pleomorphic adenoma (Ca Ex PA). 48 cases (80%) showed positive expression, in which benign tumors exhibited relatively increased reactivity (85.7%) as compared to the malignant tumors (78.3%). 10 PA, 2 MY, 20 ACC, 9 MEC, 6 AC and 1 Ca Ex PA expressed E-cadherin. Negative expression was evident in CA, ACC, MEC and AC. Statistically significant reduction in reactivity was evident in mucoepidermoid carcinoma and adenocarcinoma, when compared to pleomorphic adenoma.
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PMID:Benign, malignant salivary gland tumors: comparison of immunohistochemical expression of e-cadherin. 1895 11

Signet-ring cell carcinoma (SRCC) developing in the colorectum (CR) is infrequently identified at an early stage (no deeper than submucosa). Most such examples involve the submucosa. Merely 13 cases of intramucosal CR SRCC are at hand. We recently had the opportunity to study a specimen with two synchronous early-stage SRCC, developed in a 65-year-old hereditary nonpolyposis colorectal cancer male patient with a known disease-causing mutation in MLH1. A right hemicolectomy specimen comprised a 15-mm intramucosal cecal lesion, featuring zones of conventional tubular adenoma and intraepithelial SRCC as well as tumor cells multifocally permeating the lamina propria and a 12-mm submucosally expanding SRCC of the ascending colon. The intramucosal and intraepithelial as well as stromal lesional cells displayed a normal membranous expression of beta-catenin and E-cadherin; submucosally infiltrating cells featured alterations in this complex with loss of membranous expression of both proteins and a shift with nuclear accumulation of beta-catenin, suggesting a disruption of the Wingless signaling pathway taking place at the transition from the intramucosal to the submucosal level.
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PMID:HNPCC-associated synchronous early-stage signet-ring cell carcinomas of colonic origin. A comparative morphological and immunohistochemical study of an intramucosal and a submucosal example. 1900 94

Modifications in cell surface glycosylation affecting cell adhesion are common characteristics of transformed cells. This study characterizes the N-glycosylation profile of E-cadherin in models of canine mammary gland adenoma and carcinoma evaluating the importance of these glycosylation modifications in the malignant phenotype. Our results show that the pattern of E-cadherin N-glycosylation in mammary carcinoma is characterized by highly branched N-glycans, increase in sialylation and an expression of few high mannose structures. Detailed mass spectrometry analysis demonstrated a new N-glycosylation site containing a potential complex type N-glycan in E-cadherin from a mammary carcinoma cell line. Our study demonstrates the importance of E-cadherin N-glycans in the process of tumor development and in the transformation to the malignant phenotype.
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PMID:Role of E-cadherin N-glycosylation profile in a mammary tumor model. 1915 17

It is thought that dysregulation of E-cadherin, syndecan-1 (CD138) and Ets-1 is involved in carcinoma development. E-cadherin is an important epithelial cell adhesion molecule; syndecan-1 (CD138) is a regulatory proteoglycan in both cell-cell and cell-matrix adhesion and Ets-1 is a proto-oncogene and transcription factor, which takes part in extracellular matrix remodeling. Our goal was to study the changes in the expression of these molecules during colon carcinoma development and progression. We tested 117 colon adenomas and 149 de novo and ex adenoma carcinomas of the colon, using the Ultravision Polymer system. The positive reaction rate was 100% for E-cadherin, 98.3% for syndecan-1 and 22.4% for Ets-1 in adenomas, while in carcinomas it was 88.5%, 62.4% and 56.3% respectively. We found decreasing expression of E-cadherin and syndecan-1 throughout colon carcinoma progression and an opposite regulation for the Ets-1 protein. Decrease in expression of syndecan-1 is more pronounced in carcinomas compared to E-cadherin. De novo carcinomas have lower E-cadherin and syndecan-1 expression, and higher Ets-1 expression compared to ex adenoma carcinomas. These findings support the hypothesis that there are differences in the carcinogenesis of these tumors.
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PMID:An immunohistochemical study of colon adenomas and carcinomas: E-cadherin, Syndecan-1, Ets-1. 1925 33

Carcinoma ex-pleomorphic adenoma (CXPA) is an aggressive salivary gland malignancy, usually derived from a long-standing or a recurrent benign tumor, the pleomorphic adenoma (PA). In the context of dynamic reciprocity, changes in the composition and structure of extracellular matrix proteins and cell surface receptors have been frequently associated with dysfunctional adhesion and invasive behavior of tumor cells. It is not fully understood if these changes are involved in the conversion of PA to CXPA. In this study, different progression stages of CXPA were investigated regarding the expression of the major extracellular matrix proteins, collagen type I, and of E-cadherin and beta-catenin, the components of adherens junctions. By immunohistochemical analysis, we have demonstrated that direct contact of tumor cells with fibrillar type I collagen, particularly near the invasive front and in invasive areas prevailing small nests of CXPA cells, could be associated with reduced expression of the E-cadherin and beta-catenin adhesion molecules and with invasive behavior of epithelial, but not of CXPA with myoepithelial component. Our results also suggested that this association could depend on the organization of collagen molecules, being prevented by high-order polymeric structures. These findings could implicate the local microenvironment in the transition from the premalignant PA to invasive CXPA.
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PMID:Collagen type I may influence the expression of E-cadherin and beta-catenin in carcinoma ex-pleomorphic adenoma. 1927 72


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