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Beta-catenin--a linchpin in colorectal carcinogenesis?Wong NA; Pignatelli MAm J Pathol 2002[Feb]; 160 (2): 389-401An important role for beta-catenin pathways in colorectal carcinogenesis was first suggested by the protein's association with adenomatous polyposis coli (APC) protein, and by evidence of dysregulation of beta-catenin protein expression at all stages of the adenoma-carcinoma sequence. Recent studies have, however, shown that yet more components of colorectal carcinogenesis are linked to beta-catenin pathways. Pro-oncogenic factors that also release beta-catenin from the adherens complex and/or encourage translocation to the nucleus include ras, epidermal growth factor (EGF), c-erbB-2, PKC-betaII, MUC1, and PPAR-gamma, whereas anti-oncogenic factors that also inhibit nuclear beta-catenin signaling include transforming growth factor (TGF)-beta, retinoic acid, and vitamin D. Association of nuclear beta-catenin with the T cell factor (TCF)/lymphoid enhancer factor (LEF) family of transcription factors promotes the expression of several compounds that have important roles in the development and progression of colorectal carcinoma, namely: c-myc, cyclin D1, gastrin, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-7, urokinase-type plasminogen activator receptor (aPAR), CD44 proteins, and P-glycoprotein. Finally, genetic aberrations of several components of the beta-catenin pathways, eg, Frizzled (Frz), AXIN, and TCF-4, may potentially contribute to colorectal carcinogenesis. In discussing the above interactions, this review demonstrates that beta-catenin represents a key molecule in the development of colorectal carcinoma.|*Trans-Activators[MESH]|ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics/metabolism[MESH]|Adenoma/pathology/*physiopathology[MESH]|Adenomatous Polyposis Coli Protein/genetics/metabolism[MESH]|Animals[MESH]|Calcium-Calmodulin-Dependent Protein Kinases/metabolism[MESH]|Carcinoma/pathology/*physiopathology[MESH]|Colorectal Neoplasms/pathology/*physiopathology[MESH]|Cyclin D1/genetics/metabolism[MESH]|Cyclooxygenase 2[MESH]|Cytoskeletal Proteins/genetics/*metabolism[MESH]|Gastrins/genetics/metabolism[MESH]|Glycogen Synthase Kinase 3[MESH]|Humans[MESH]|Hyaluronan Receptors/genetics/metabolism[MESH]|Intestinal Mucosa/cytology[MESH]|Isoenzymes/genetics/metabolism[MESH]|Matrix Metalloproteinase 7/genetics/metabolism[MESH]|Membrane Proteins[MESH]|Prostaglandin-Endoperoxide Synthases/genetics/metabolism[MESH]|Proto-Oncogene Proteins/genetics/metabolism[MESH]|Receptors, Cell Surface/genetics/metabolism[MESH]|Receptors, Urokinase Plasminogen Activator[MESH]|Signal Transduction/*physiology[MESH]|beta Catenin[MESH] |
