The Plus Side of CIN

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Science  02 Jan 2004:
Vol. 303, Issue 5654, pp. 16
DOI: 10.1126/science.303.5654.16d

Tumor cells often exhibit dramatic karyotypic changes, including gains and losses of chromosomes. This chromosomal instability (CIN) has been proposed to play a role in tumor progression, and the mechanism(s) by which it arises are of great interest. Studying a series of CIN+ colorectal cancer cell lines, Green and Kaplan identified aberrations in the mitotic spindle, the cellular apparatus that ensures proper chromosome segregation during cell division. Notably, the CIN+ cells showed inefficient attachment of spindle microtubule plus-ends to the chromosome kinetochores and cell cortex, leading to defects in chromosome alignment during metaphase. Similar defects were observed when a mutant version of the adenomatous polyposis coli (APC) tumor suppressor protein was introduced into normal cells. These results add to the accumulating evidence (see Reports, 12 September 2003, p.1547) that APC, which was once thought to function in tumorigenesis primarily through its effects on the Wnt signal transduction pathway, may also play a critical role in the positioning and function of the mitotic spindle. — PAK

J. Cell Biol. 163, 949 (2003).

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