title: Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon.
abstract: Mutations in the APC tumor suppressor gene are present in approximately 85% of colorectal tumors and are thought to contribute early in the process of tumorigenesis. The truncated protein resulting from most APC mutations can lead to elevated beta-catenin levels in colon tumor cells. APC and associated proteins thus form a beta-catenin regulatory complex, with axin playing a key role. Although cell culture studies have revealed intriguing aspects of this complex, little characterization has been done in human colonocytes, the target tissue of colon carcinogenesis. The present study of intact human colon crypts, adenomatous polyps, and adenocarcinomas focuses on subcellular localization of some key elements of the complex: beta-catenin, APC, axin, and axin2. We examined endogenous protein localization within the framework of three-dimensional tissue architecture by using laser scanning confocal microscopy, and immunofluorescence staining of whole-mount fixed tissue from more than 50 patients. Expression patterns suggest that APC and axin colocalize in the nucleus and at lateral cell borders, and show that axin2 is limited to the nucleus. Altered nuclear expression of axin seen in colon polyps and carcinomas may be a consequence of the loss of full-length APC and the advent of nuclear beta-catenin. The observation of nuclear beta-catenin in fewer than half of carcinoma images and only rarely in polyps indicates that nuclear translocation of beta-catenin may not be an immediate consequence of the loss of APC.
authors.affiliation: Eccles Institute of Human Genetics and Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA. chris.anderson@genetics.utah.edu
authors.forename: Christine B
authors.initials: CB
authors.lastname: Anderson
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Neufeld
authors.forename: Raymond L
authors.initials: RL
authors.lastname: White
mesh_terms: D018256:Adenomatous Polyps / Q000378:metabolism; D000818:Animals; D060466:Axin Protein; D002467:Cell Nucleus; D003106:Colon / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D017491:Genes, APC; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012097:Repressor Proteins; D013347:Subcellular Fractions / Q000378:metabolism*; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
chemical_list: D060466:Axin Protein; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin