PubMed:10027390 JSONTXT

{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":86,"end":104},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":548,"end":574},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":758,"end":766},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":994,"end":1002},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":1176,"end":1184},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":1530,"end":1538},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":1572,"end":1580},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T8","span":{"begin":1721,"end":1729},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":1826,"end":1831},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0005105"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0021055"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0005105"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"0005105"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"0005105"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"0005105"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"0005105"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"0005105"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"0005070"}],"text":"Frequent nuclear/cytoplasmic localization of beta-catenin without exon 3 mutations in malignant melanoma.\nBeta-Catenin has a critical role in E-cadherin-mediated cell-cell adhesion, and it also functions as a downstream signaling molecule in the wnt pathway. Mutations in the putative glycogen synthase kinase 3beta phosphorylation sites near the beta-catenin amino terminus have been found in some cancers and cancer cell lines. The mutations render beta-catenin resistant to regulation by a complex containing the glycogen synthase kinase 3beta, adenomatous polyposis coli, and axin proteins. As a result, beta-catenin accumulates in the cytosol and nucleus and activates T-cell factor/ lymphoid enhancing factor transcription factors. Previously, 6 of 27 melanoma cell lines were found to have beta-catenin exon 3 mutations affecting the N-terminal phosphorylation sites (Rubinfeld B, Robbins P, Elgamil M, Albert I, Porfiri E, Polakis P: Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science 1997, 275:1790-1792). To assess the role of beta-catenin defects in primary melanomas, we undertook immunohistochemical and DNA sequencing studies in 65 melanoma specimens. Nuclear and/or cytoplasmic localization of beta-catenin, a potential indicator of wnt pathway activation, was seen focally within roughly one third of the tumors, though a clonal somatic mutation in beta-catenin was found in only one case (codon 45 Ser--\u003ePro). Our findings demonstrate that beta-catenin mutations are rare in primary melanoma, in contrast to the situation in melanoma cell lines. Nonetheless, activation of beta-catenin, as indicated by its nuclear and/or cytoplasmic localization, appears to be frequent in melanoma, and in some cases, it may reflect focal and transient activation of the wnt pathway within the tumor."}

{"project":"PennBioIE","denotations":[{"id":"T1","span":{"begin":45,"end":57},"obj":"protein"},{"id":"T2","span":{"begin":66,"end":72},"obj":"protein"},{"id":"T3","span":{"begin":110,"end":118},"obj":"protein"},{"id":"T4","span":{"begin":142,"end":152},"obj":"protein"},{"id":"T5","span":{"begin":246,"end":249},"obj":"protein"},{"id":"T6","span":{"begin":285,"end":315},"obj":"protein"},{"id":"T7","span":{"begin":347,"end":359},"obj":"protein"},{"id":"T8","span":{"begin":451,"end":463},"obj":"protein"},{"id":"T9","span":{"begin":516,"end":546},"obj":"protein"},{"id":"T10","span":{"begin":548,"end":574},"obj":"protein"},{"id":"T11","span":{"begin":580,"end":584},"obj":"protein"},{"id":"T12","span":{"begin":608,"end":620},"obj":"protein"},{"id":"T13","span":{"begin":674,"end":687},"obj":"protein"},{"id":"T14","span":{"begin":689,"end":714},"obj":"protein"},{"id":"T15","span":{"begin":797,"end":809},"obj":"protein"},{"id":"T16","span":{"begin":810,"end":816},"obj":"protein"},{"id":"T17","span":{"begin":959,"end":971},"obj":"protein"},{"id":"T18","span":{"begin":1067,"end":1079},"obj":"protein"},{"id":"T19","span":{"begin":1239,"end":1251},"obj":"protein"},{"id":"T20","span":{"begin":1278,"end":1281},"obj":"protein"},{"id":"T21","span":{"begin":1395,"end":1407},"obj":"protein"},{"id":"T22","span":{"begin":1436,"end":1444},"obj":"protein"},{"id":"T23","span":{"begin":1445,"end":1448},"obj":"protein"},{"id":"T24","span":{"begin":1451,"end":1454},"obj":"protein"},{"id":"T25","span":{"begin":1487,"end":1499},"obj":"protein"},{"id":"T26","span":{"begin":1620,"end":1632},"obj":"protein"},{"id":"T27","span":{"begin":1803,"end":1806},"obj":"protein"}],"text":"Frequent nuclear/cytoplasmic localization of beta-catenin without exon 3 mutations in malignant melanoma.\nBeta-Catenin has a critical role in E-cadherin-mediated cell-cell adhesion, and it also functions as a downstream signaling molecule in the wnt pathway. Mutations in the putative glycogen synthase kinase 3beta phosphorylation sites near the beta-catenin amino terminus have been found in some cancers and cancer cell lines. The mutations render beta-catenin resistant to regulation by a complex containing the glycogen synthase kinase 3beta, adenomatous polyposis coli, and axin proteins. As a result, beta-catenin accumulates in the cytosol and nucleus and activates T-cell factor/ lymphoid enhancing factor transcription factors. Previously, 6 of 27 melanoma cell lines were found to have beta-catenin exon 3 mutations affecting the N-terminal phosphorylation sites (Rubinfeld B, Robbins P, Elgamil M, Albert I, Porfiri E, Polakis P: Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science 1997, 275:1790-1792). To assess the role of beta-catenin defects in primary melanomas, we undertook immunohistochemical and DNA sequencing studies in 65 melanoma specimens. Nuclear and/or cytoplasmic localization of beta-catenin, a potential indicator of wnt pathway activation, was seen focally within roughly one third of the tumors, though a clonal somatic mutation in beta-catenin was found in only one case (codon 45 Ser--\u003ePro). Our findings demonstrate that beta-catenin mutations are rare in primary melanoma, in contrast to the situation in melanoma cell lines. Nonetheless, activation of beta-catenin, as indicated by its nuclear and/or cytoplasmic localization, appears to be frequent in melanoma, and in some cases, it may reflect focal and transient activation of the wnt pathway within the tumor."}

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":399,"end":406},"obj":"HP_0002664"},{"id":"T2","span":{"begin":411,"end":417},"obj":"HP_0002664"},{"id":"T3","span":{"begin":758,"end":766},"obj":"HP_0002861"},{"id":"T4","span":{"begin":994,"end":1002},"obj":"HP_0002861"},{"id":"T5","span":{"begin":1099,"end":1108},"obj":"HP_0002861"},{"id":"T6","span":{"begin":1176,"end":1184},"obj":"HP_0002861"},{"id":"T7","span":{"begin":1351,"end":1357},"obj":"HP_0002664"},{"id":"T8","span":{"begin":1375,"end":1391},"obj":"HP_0001428"},{"id":"T9","span":{"begin":1530,"end":1538},"obj":"HP_0002861"},{"id":"T10","span":{"begin":1572,"end":1580},"obj":"HP_0002861"},{"id":"T11","span":{"begin":1721,"end":1729},"obj":"HP_0002861"},{"id":"T12","span":{"begin":1826,"end":1831},"obj":"HP_0002664"}],"text":"Frequent nuclear/cytoplasmic localization of beta-catenin without exon 3 mutations in malignant melanoma.\nBeta-Catenin has a critical role in E-cadherin-mediated cell-cell adhesion, and it also functions as a downstream signaling molecule in the wnt pathway. Mutations in the putative glycogen synthase kinase 3beta phosphorylation sites near the beta-catenin amino terminus have been found in some cancers and cancer cell lines. The mutations render beta-catenin resistant to regulation by a complex containing the glycogen synthase kinase 3beta, adenomatous polyposis coli, and axin proteins. As a result, beta-catenin accumulates in the cytosol and nucleus and activates T-cell factor/ lymphoid enhancing factor transcription factors. Previously, 6 of 27 melanoma cell lines were found to have beta-catenin exon 3 mutations affecting the N-terminal phosphorylation sites (Rubinfeld B, Robbins P, Elgamil M, Albert I, Porfiri E, Polakis P: Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science 1997, 275:1790-1792). To assess the role of beta-catenin defects in primary melanomas, we undertook immunohistochemical and DNA sequencing studies in 65 melanoma specimens. Nuclear and/or cytoplasmic localization of beta-catenin, a potential indicator of wnt pathway activation, was seen focally within roughly one third of the tumors, though a clonal somatic mutation in beta-catenin was found in only one case (codon 45 Ser--\u003ePro). Our findings demonstrate that beta-catenin mutations are rare in primary melanoma, in contrast to the situation in melanoma cell lines. Nonetheless, activation of beta-catenin, as indicated by its nuclear and/or cytoplasmic localization, appears to be frequent in melanoma, and in some cases, it may reflect focal and transient activation of the wnt pathway within the tumor."}