Chromokinesins: Possible Generators of Cancer-Associated Aneuploidy
Abstract
Aneuploidy occurs with high frequency in breast cancer cells, and an aneuploidy increase is positively correlated with the transition from pre-malignant to metastatic cancer. Chromokinesins, a family of chromosome-associated microtubule motors, are potential generators of aneuploidy since they are believed to participate in spindle morphogenesis and chromosome movements during mitosis. Our hypothesis is that inhibition of chromokinesin activity increases the aneuploid frequency in cultured cells. Five different chromokinesins were knocked-down individually or in combination in cultured S2 cells using RNAi. Individual and combined chromokinesin RNAi can result in a statistically significant increase of kinetochore number (ie, aneuploidy). Generally, inhibition of multiple chromokinesins has a stronger affect on aneuploidy than inihibition of individual chromokinesins, but the multiple inhibition affects are not strictly additive. In addition, RNAi of some chromokinesins markedly increased the mitotic index and the frequency of multi-nucleation. Together, these results support the hypothesis that chromokinesin inhibition can lead to aneuploidy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2005
- Accession Number
- ADA447643
Entities
People
- D.J. Sharp
- Daniel W. Buster
Organizations
- Albert Einstein College of Medicine