Details
- Autor(en) / Beteiligte
- Titel
- Morphological and transcriptional responses of untransformed intestinal epithelial cells to an oncogenic β-catenin protein
- Ist Teil von
- Oncogene, 2005-04, Vol.24 (19), p.3141-3153
- Ort / Verlag
- Basingstoke: Nature Publishing
- Erscheinungsjahr
- 2005
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Aberrant transactivation of a certain set of target genes by the beta-catenin and T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor complexes has been implicated in the process of intestinal epithelial cells entering early colorectal carcinogenesis. A rat intestinal epithelial cell line IEC6 became elongated, extended protrusions at cell periphery, and increased stress fibers and focal contacts upon the induction of beta-catenin protein stabilized by deletion of the N-terminal glycogen synthase kinase-3beta (GSKbeta) phosphorylation sites (beta-catenin DeltaN89). We used the GeneChiptrade mark oligonucleotide microarray system to examine approximately 24 000 genes and identified 13 genes whose expression was altered during the course of this morphological transformation. Those genes included known negative regulators of the Wnt signaling pathway, Sfrp4 and Axin2; extracellular matrix and related molecule, Hxb and Crtl1; cell adhesion and cytoskeletal proteins, Podxl, Igaf4, and Itab6; and molecules involved in the insulin and insulin-like growth factor (IGF) signaling pathways, Enpp1, Igfbp2, and Sgk. We report the finding that insulin-like growth factor-binding protein-2 (IGFBP2) is a direct target gene of the beta-catenin and TCF/LEF complexes. The IGFBP2 protein interacts with integrins. Disruption of the multigene network system regulating cell adhesion and cytoskeleton may be crucial in the initiation of colorectal carcinogenesis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232eISSN: 1476-5594DOI: 10.1038/sj.onc.1208517Titel-ID: cdi_proquest_miscellaneous_17843860
- Format
- –
- Schlagworte
- Adenoma - metabolism, Animals, beta Catenin, Biological and medical sciences, Carcinogenesis, Cell Adhesion, Cell adhesion & migration, Cell adhesion molecules, Cell Line, Cell Line, Transformed, Cell Line, Tumor, Cell physiology, Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes, Cell Transformation, Neoplastic, Cells, Cultured, Chromatin Immunoprecipitation, Colon - metabolism, Colorectal Neoplasms - metabolism, Cytoskeletal Proteins - metabolism, Cytoskeleton, DNA microarrays, DNA-Binding Proteins - metabolism, Epithelial cells, Epithelial Cells - metabolism, Extracellular matrix, Extracellular Matrix - metabolism, Fundamental and applied biological sciences. Psychology, Gene Expression Regulation, Neoplastic, Genes, Reporter, Glycogen, Glycogen synthase kinase 3, Glycogen Synthase Kinase 3 - metabolism, Glycogen Synthase Kinase 3 beta, HeLa Cells, Humans, Immunohistochemistry, Insulin, Insulin-like growth factor-binding protein 2, Insulin-like growth factors, Integrins, Intercellular Signaling Peptides and Proteins - metabolism, Intestine, Intestine, Small - metabolism, Intestines - metabolism, Kinases, LEF/TCF protein, Luciferases - metabolism, Lymphocytes T, Lymphoid Enhancer-Binding Factor 1, Male, Mice, Mice, Inbred C57BL, Microscopy, Fluorescence, Molecular and cellular biology, Molecular genetics, Morphology, Oligonucleotide Array Sequence Analysis, Oligonucleotides, Phosphorylation, Protein Structure, Tertiary, Proteins, Rats, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Time Factors, Trans-Activators - metabolism, Transcription factors, Transcription Factors - metabolism, Transcription, Genetic, Transcription. Transcription factor. Splicing. Rna processing, Wnt protein, Wnt Proteins, β-Catenin