Article: Beta-catenin--a linchpin in colorectal carcinogenesis?
The American journal of pathology
2002 Volume 160, Issue 2, Page(s) 389–401
Abstract: An 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 ... ...
| Abstract | An 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. |
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| MeSH term(s) | ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; Adenoma/pathology ; Adenoma/physiopathology ; Adenomatous Polyposis Coli Protein/genetics ; Adenomatous Polyposis Coli Protein/metabolism ; Animals ; Calcium-Calmodulin-Dependent Protein Kinases/metabolism ; Carcinoma/pathology ; Carcinoma/physiopathology ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/physiopathology ; Cyclin D1/genetics ; Cyclin D1/metabolism ; Cyclooxygenase 2 ; Cytoskeletal Proteins/genetics ; Cytoskeletal Proteins/metabolism ; Gastrins/genetics ; Gastrins/metabolism ; Glycogen Synthase Kinase 3 ; Humans ; Hyaluronan Receptors/genetics ; Hyaluronan Receptors/metabolism ; Intestinal Mucosa/cytology ; Isoenzymes/genetics ; Isoenzymes/metabolism ; Matrix Metalloproteinase 7/genetics ; Matrix Metalloproteinase 7/metabolism ; Membrane Proteins ; Prostaglandin-Endoperoxide Synthases/genetics ; Prostaglandin-Endoperoxide Synthases/metabolism ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/metabolism ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/metabolism ; Receptors, Urokinase Plasminogen Activator ; Signal Transduction/physiology ; Trans-Activators ; beta Catenin | |||||
| Chemical Substances | ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Adenomatous Polyposis Coli Protein ; CTNNB1 protein, human ; Cytoskeletal Proteins ; Gastrins ; Hyaluronan Receptors ; Isoenzymes ; Membrane Proteins ; PLAUR protein, human ; Proto-Oncogene Proteins ; Receptors, Cell Surface ; Receptors, Urokinase Plasminogen Activator ; Trans-Activators ; beta Catenin ; Cyclin D1 (136601-57-5) ; Cyclooxygenase 2 (EC 1.14.99.1) ; PTGS2 protein, human (EC 1.14.99.1) ; Prostaglandin-Endoperoxide Synthases (EC 1.14.99.1) ; Calcium-Calmodulin-Dependent Protein Kinases (EC 2.7.11.17) ; Glycogen Synthase Kinase 3 (EC 2.7.11.26) ; Matrix Metalloproteinase 7 (EC 3.4.24.23) | |||||
| Language | English | |||||
| Publishing date | 2002-02-06 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Review | |||||
| ZDB-ID | 2943-9 | |||||
| ISSN | 1525-2191 ; 0002-9440 | |||||
| ISSN (online) | 1525-2191 | |||||
| ISSN | 0002-9440 | |||||
| DOI | 10.1016/s0002-9440(10)64856-0 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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