Journal
JOURNAL OF CELL BIOLOGY
Volume 180, Issue 4, Pages 665-672Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200712029
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Funding
- NIGMS NIH HHS [R37 GM051542, GM51542, T32 GM008704, R01 GM051542] Funding Source: Medline
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Solid tumors can be highly aneuploid and many display high rates of chromosome missegregation in a phenomenon called chromosomal instability (CIN). In principle, aneuploidy is the consequence of CIN, but the relationship between CIN and aneuploidy has not been clearly defined. In this study, we use live cell imaging and clonal cell analyses to evaluate the fidelity of chromosome segregation in chromosomally stable and unstable human cells. We show that improper microtubule-chromosome attachment (merotely) is a cause of chromosome missegregation in unstable cells and that increasing chromosome missegregation rates by elevating merotely during consecutive mitoses generates CIN in otherwise stable, near-diploid cells. However, chromosome missegregation compromises the proliferation of diploid cells, indicating that phenotypic changes that permit the propagation of nondiploid cells must combine with elevated chromosome missegregation rates to generate aneuploid cells with CIN.
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