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J Cell Biol. 2007 Jan 15;176(2):183-95.

Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis.

Author information

1
Division of Cell and Developmental Biology, University of Dundee, Dundee DD1 5EH, Scotland, UK.

Erratum in

  • J Cell Biol. 2007 Jan 29;176(3):369.

Abstract

Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene initiate a majority of colorectal cancers. Acquisition of chromosomal instability is an early event in these tumors. We provide evidence that the loss of APC leads to a partial loss of interkinetochore tension at metaphase and alters mitotic progression. Furthermore, we show that inhibition of APC in U2OS cells compromises the mitotic spindle checkpoint. This is accompanied by a decrease in the association of the checkpoint proteins Bub1 and BubR1 with kinetochores. Additionally, APC depletion reduced apoptosis. As expected from this combination of defects, tetraploidy and polyploidy are consequences of APC inhibition in vitro and in vivo. The removal of APC produced the same defects in HCT116 cells that have constitutively active beta-catenin. These data show that the loss of APC immediately induces chromosomal instability as a result of a combination of mitotic and apoptotic defects. We suggest that these defects amplify each other to increase the incidence of tetra- and polyploidy in early stages of tumorigenesis.

PMID:
17227893
PMCID:
PMC2063938
DOI:
10.1083/jcb.200610099
[Indexed for MEDLINE]
Free PMC Article

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