- Paper Report
- Open Access
What centrosomes can teach us about tumor progression
- Karen Schmeichel1
© Biomed Central Ltd 2002
- Received: 19 March 2002
- Accepted: 8 April 2002
- Published: 1 December 2002
- Aneuploidy, breast tumor progression, centrosomes, chrosomal instability, microtubules, p53
During mitosis, centrosomes organize microtubules into spindle structures that mediate proper chromosomal segregation. Increased centrosome number, a characteristic common to a majority of breast tumors, is thought to cause chromosomal mis-segregations and thus lead to tumor aneuploidy. Because interphase centrosomes nucleate and organize the microtubule cytoskeleton, centrosome abnormalities could also contribute to cellular malignancy by disrupting overall cellular architecture. Given the dual significance of the centrosome, the authors examined the relationship between centrosomes (i.e. number, size and activity) and chromosomal instability (CIN), p53 mutation, tissue differentiation and aneuploidy in a total of 27 tissue samples from either normal breast (n = 7) or from tumors of five histologic grades ( diploid [n = 3], monosomy 17 [n = 3], stable aneuploid [n = 5], unstable aneuploid [n = 9]).
In primary breast tissue samples, amplification of both centrosome size and number correlated directly with CIN and aneuploidy. This correlation was independent of p53 status, thus centrosome amplifications driving CIN may be due to molecular lesions other than p53 mutation. Alterations in centrosome function, as measured by increased microtubule nucleation capacity, did not correlate with centrosome amplification, CIN and aneuploidy. However, nucleation activity increased with loss of tissue differentiation; undifferentiated aneuploid tumors, especially those with p53 mutations, showed a higher level of nucleating activity than lower grade tumors. Finally, centrosome amplification was detected in in situ ductal carcinomas, suggesting that centrosome defects drive chromosomal irregularities at an early stage in tumor progression.