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dc.contributor.authorWilson, James W
dc.contributor.authorDeed, Richard W
dc.contributor.authorInoue, Toshiaki
dc.contributor.authorBalzi, Manuela
dc.contributor.authorBecciolini, Aldo
dc.contributor.authorFaraoni, Paola
dc.contributor.authorPotten, Christopher S
dc.contributor.authorNorton, John D
dc.date.accessioned2009-11-06T11:52:54Z
dc.date.available2009-11-06T11:52:54Z
dc.date.issued2001-12-15
dc.identifier.citationExpression of Id helix-loop-helix proteins in colorectal adenocarcinoma correlates with p53 expression and mitotic index. 2001, 61 (24):8803-10 Cancer Res.en
dc.identifier.issn0008-5472
dc.identifier.pmid11751402
dc.identifier.urihttp://hdl.handle.net/10541/85534
dc.description.abstractId helix-loop-helix (HLH) proteins function as regulators of cell growth and differentiation and when overexpressed can induce malignant transformation. In a series of 34 cases of primary human colorectal adenocarcinoma, immunoreactivity for Id1, Id2, and Id3 was found to be significantly elevated in tumor compared with normal mucosa (P = 0.001 for Id1 and Id2; P = 0.002 for Id3). No elevation of Id expression was observed in 17 cases of adenoma. Expression of Id1 and to a lesser extent of Id2 was correlated with mitotic index (P = 0.005 for Id1; P = 0.042 for Id2) in human adenocarcinomas, and expression of all three Id proteins was correlated with p53 immunoreactivity (a marker of mutational 'inactivation' of p53 function; P = 0.002 for Id1; P = 0.006 for Id2; P = 0.016 for Id3). In normal intestinal mucosa of p53-null mice and in spontaneous tumors arising in Min+/- mice, expression of all three Id proteins was also found to be up-regulated. Antisense oligonucleotide blockade of Id protein expression inhibited the proliferation of human adenocarcinoma cells. Enforced, ectopic expression of the E47 basic HLH (bHLH) protein in human adenocarcinoma cell lines efficiently sequestered endogenous Id proteins as Id-bHLH heterodimers, as shown by coimmunoprecipitation and subcellular colocalization studies. This led to growth arrest of the cells. Enforced overexpression of a mutant E47 protein, deficient in transactivation and DNA binding function, also partially inhibited cell growth. Taken together, these data imply that deregulated expression of Id proteins in colorectal adenocarcinoma arises at least in part as a consequence of loss of p53 function and contributes to the uncontrolled proliferation of tumor cells in colorectal cancer.
dc.language.isoenen
dc.subjectColorectal Canceren
dc.subjectCultured Tumour Cellsen
dc.subjectTumour Suppressor Protein p53en
dc.subject.meshAdenocarcinoma
dc.subject.meshAnimals
dc.subject.meshBasic Helix-Loop-Helix Transcription Factors
dc.subject.meshCell Division
dc.subject.meshColon
dc.subject.meshColorectal Neoplasms
dc.subject.meshDNA-Binding Proteins
dc.subject.meshDimerization
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshHelix-Loop-Helix Motifs
dc.subject.meshHumans
dc.subject.meshImmunohistochemistry
dc.subject.meshInhibitor of Differentiation Protein 1
dc.subject.meshIntestinal Mucosa
dc.subject.meshMice
dc.subject.meshMitotic Index
dc.subject.meshOligonucleotides, Antisense
dc.subject.meshPrecipitin Tests
dc.subject.meshRepressor Proteins
dc.subject.meshTranscription Factors
dc.subject.meshTumor Cells, Cultured
dc.subject.meshTumor Suppressor Protein p53
dc.titleExpression of Id helix-loop-helix proteins in colorectal adenocarcinoma correlates with p53 expression and mitotic index.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Epithelial Biology Group, Paterson Institute for Cancer Research, Christie Hospital, National Health Service Trust, Manchester M20 4BX, United Kingdom.en
dc.identifier.journalCancer Researchen
html.description.abstractId helix-loop-helix (HLH) proteins function as regulators of cell growth and differentiation and when overexpressed can induce malignant transformation. In a series of 34 cases of primary human colorectal adenocarcinoma, immunoreactivity for Id1, Id2, and Id3 was found to be significantly elevated in tumor compared with normal mucosa (P = 0.001 for Id1 and Id2; P = 0.002 for Id3). No elevation of Id expression was observed in 17 cases of adenoma. Expression of Id1 and to a lesser extent of Id2 was correlated with mitotic index (P = 0.005 for Id1; P = 0.042 for Id2) in human adenocarcinomas, and expression of all three Id proteins was correlated with p53 immunoreactivity (a marker of mutational 'inactivation' of p53 function; P = 0.002 for Id1; P = 0.006 for Id2; P = 0.016 for Id3). In normal intestinal mucosa of p53-null mice and in spontaneous tumors arising in Min+/- mice, expression of all three Id proteins was also found to be up-regulated. Antisense oligonucleotide blockade of Id protein expression inhibited the proliferation of human adenocarcinoma cells. Enforced, ectopic expression of the E47 basic HLH (bHLH) protein in human adenocarcinoma cell lines efficiently sequestered endogenous Id proteins as Id-bHLH heterodimers, as shown by coimmunoprecipitation and subcellular colocalization studies. This led to growth arrest of the cells. Enforced overexpression of a mutant E47 protein, deficient in transactivation and DNA binding function, also partially inhibited cell growth. Taken together, these data imply that deregulated expression of Id proteins in colorectal adenocarcinoma arises at least in part as a consequence of loss of p53 function and contributes to the uncontrolled proliferation of tumor cells in colorectal cancer.


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