Adenomatous polyposis coli/beta-catenin interaction and downstream targets: altered gene expression in gastrointestinal tumors.
Gastrointestinal cancer affects 250,000 Americans a year with nearly half of those cases being colorectal cancer. The Wnt pathway is activated in most spontaneous and familial colorectal cancers and has been implicated in tumor formation at other sites in the gastrointestinal tract. In human tumors, the Wnt pathway is most often altered by mutations affecting certain components of this signal transduction cascade-the adenomatous polyposis coli (APC) tumor suppressor gene or the ss-catenin gene. Perturbations in the function of either protein lead to altered gene regulation through the interaction of ss-catenin with T-cell factor (Tcf)/lymphoid enhancer binding protein (Lef) transcription factors. This review will discuss the Wnt pathway, examine the mutations of its components that are found in human cancer, and discuss the known downstream gene targets.
Clements
Wilson M
WM
Howard Hughes Medical Institute, and Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Lowy
Andrew M
AM
Groden
Joanna
J
D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000503:physiopathology; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000494:pharmacology; D015820:Cadherins; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008024:Ligands; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000494:pharmacology*; D015398:Signal Transduction; D015534:Trans-Activators / Q000096:biosynthesis* / Q000494:pharmacology*; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D008024:Ligands; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D011505:Protein-Tyrosine Kinases