Cited by 108Wnt/β-catenin signaling in development and cancerGenetic factors in colorectal cancerColorectal Cancer Treatments and Studies

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Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon

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Anderson, Christine B., Neufeld, Kristi L., White, Raymond L.·2002·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.122235399PMC PMC124359

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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…

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Authors: Anderson, C. B., Neufeld, K. L., & White, R. L.
Affiliations: University of Utah (US)
ORCID: Neufeld, Kristi L.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2002-06-18
Volume: 99
Issue: 13
Pages: 8683-8688
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.122235399
PMC: PMC124359
OpenAlex: W2058194940
Cited by: 108
References: 34
Citations by year: 2026: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 6 · 2015: 5 · 2014: 9 · 2013: 9 · 2012: 7
FWCI: 1.86
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Huntsman Cancer Institute
National Institutes of Health (5p01ca073992-15)
National Cancer Institute (P01‐CA073992, 5P01 CA73992-02)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Keywords: Wnt signaling, β-catenin, Axin, Axin2, subcellular protein localization, colonic crypts, adenomatous polyps, colon adenocarcinoma, colorectal carcinogenesis
MeSH terms: Animals, Cell Nucleus, Colon, Cytoskeletal Proteins, Humans, Microscopy, Fluorescence, Proteins, Proto-Oncogene Proteins, Repressor Proteins, Subcellular Fractions, Colorectal Neoplasms, Trans-Activators, Genes, APC, Adenomatous Polyps, Zebrafish Proteins, Wnt Proteins, beta Catenin, Mice, Axin Protein

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Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon

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