Abstract
Mutation of the adenomatous polyposis coli (APC) gene is an early step in the initiation of colon cancer. Because the distribution pattern of a protein within the cell can provide important clues as to function, we have used a combination of immunofluorescence microscopy and biochemical fractionation to determine the location of APC protein in epithelial cells. Immunofluorescence microscopy placed full-length APC protein in both the nucleus and the cytoplasm. The nuclear APC protein was concentrated in discrete subnuclear regions, including nucleoli, whereas the cytoplasmic APC protein concentrated at the leading edge of migrating cells. Colocalization of APC protein with rRNA confirmed a nucleolar localization. These immunocytochemical findings have been supported by cell fractionation, which demonstrated that full-length APC protein was located in both the membrane/cytoskeletal and the nuclear fractions.
MeSH Terms
Adenomatous Polyposis Coli Protein
Biological Transport
Cell Line, Transformed
Cell Nucleus/metabolism
Colonic Neoplasms/metabolism,pathology
Cytoplasm/metabolism
Cytoskeletal Proteins/metabolism
Epithelium/metabolism
Genes, APC
Microscopy, Fluorescence
Tumor Cells, Cultured
Chemicals
Adenomatous Polyposis Coli Protein
Cytoskeletal Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Neufeld K L
Huntsman Cancer Institute, University of Utah, Salt Lake City 84112, USA.
White R L
References (27)
27 references, click to expand
-
Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly.
Science. 1996 May 17;272(5264):1023-6
PMID: 8638126
-
Mutations in the APC gene and their implications for protein structure and function.
Curr Opin Genet Dev. 1995 Feb;5(1):66-71
PMID: 7749328
-
Functional interaction of beta-catenin with the transcription factor LEF-1.
Nature. 1996 Aug 15;382(6592):638-42
PMID: 8757136
-
Subcellular localization of the APC protein: immunoelectron microscopic study of the association of the APC protein with catenin.
Oncogene. 1995 Jul 6;11(1):89-96
PMID: 7624136
-
Binding of APC to the human homolog of the Drosophila discs large tumor suppressor protein.
Science. 1996 May 17;272(5264):1020-3
PMID: 8638125
-
XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos.
Cell. 1996 Aug 9;86(3):391-9
PMID: 8756721
-
Forced expression of the tumor suppressor adenomatosis polyposis coli protein induces disordered cell migration in the intestinal epithelium.
Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9588-93
PMID: 8790374
-
Chromosome analyses of human mammary epithelial cells at stages of chemical-induced transformation progression to immortality.
Cancer Genet Cytogenet. 1989 Feb;37(2):249-61
PMID: 2702624
-
Subcellular fractionation of murine erythroleukemic cells: distribution of protein kinases.
Anal Biochem. 1991 May 1;194(2):407-12
PMID: 1862942
-
Identification and characterization of the familial adenomatous polyposis coli gene.
Cell. 1991 Aug 9;66(3):589-600
PMID: 1651174
-
Identification of deletion mutations and three new genes at the familial polyposis locus.
Cell. 1991 Aug 9;66(3):601-13
PMID: 1678319
-
Identification of FAP locus genes from chromosome 5q21.
Science. 1991 Aug 9;253(5020):661-5
PMID: 1651562
-
Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients.
Science. 1991 Aug 9;253(5020):665-9
PMID: 1651563
-
Genetic heterogeneity and localization of a familial breast-ovarian cancer gene on chromosome 17q12-q21.
Am J Hum Genet. 1993 Apr;52(4):767-76
PMID: 8460642
-
The APC gene product in normal and tumor cells.
Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2846-50
PMID: 8385345
-
Dimer formation by an N-terminal coiled coil in the APC protein.
Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11109-13
PMID: 8248216
-
Association of the APC gene product with beta-catenin.
Science. 1993 Dec 10;262(5140):1731-4
PMID: 8259518
-
Association of the APC tumor suppressor protein with catenins.
Science. 1993 Dec 10;262(5140):1734-7
PMID: 8259519
-
Characteristics of somatic mutation of the adenomatous polyposis coli gene in colorectal tumors.
Cancer Res. 1994 Jun 1;54(11):3011-20
PMID: 8187091
-
Wild-type but not mutant APC associates with the microtubule cytoskeleton.
Cancer Res. 1994 Jul 15;54(14):3672-5
PMID: 8033082
-
The APC gene product associates with microtubules in vivo and promotes their assembly in vitro.
Cancer Res. 1994 Jul 15;54(14):3676-81
PMID: 8033083
-
Association of plakoglobin with APC, a tumor suppressor gene product, and its regulation by tyrosine phosphorylation.
Biochem Biophys Res Commun. 1994 Aug 30;203(1):519-22
PMID: 8074697
-
Radioimmunoassay of the APC gene product using antibodies against its middle and carboxyl regions.
Biochem Biophys Res Commun. 1995 Jan 26;206(3):909-15
PMID: 7832804
-
Embryonic axis induction by the armadillo repeat domain of beta-catenin: evidence for intracellular signaling.
J Cell Biol. 1995 Mar;128(5):959-68
PMID: 7876319
-
The APC protein and E-cadherin form similar but independent complexes with alpha-catenin, beta-catenin, and plakoglobin.
J Biol Chem. 1995 Mar 10;270(10):5549-55
PMID: 7890674
-
Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein.
Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):3046-50
PMID: 7708772
-
The adenomatous polyposis coli tumor suppressor protein localizes to plasma membrane sites involved in active cell migration.
J Cell Biol. 1996 Jul;134(1):165-79
PMID: 8698812