Chromosome 20q amplification regulates in vitro response to Kinesin-5 inhibitor.
We identified gene expression signatures predicting responsiveness to a Kinesin-5 (KIF11) inhibitor (Kinesin-5i) in cultured colon tumor cell lines. Genes predicting resistance to Kinesin-5i were enriched for those from chromosome 20q, a region of frequent amplification in a number of tumor types. siRNAs targeting genes in this chromosomal region identified AURKA, TPX2 and MYBL2 as genes whose disruption enhances response to Kinesin-5i. Taken together, our results show functional interaction between these genes, and suggest that their overexpression is involved in resistance to Kinesin-5i. Furthermore, our results suggest that patients whose tumors overexpress AURKA due to amplification of 20q will more likely resist treatment with Kinesin-5 inhibitor, and that inactivation of AURKA may sensitize these patients to treatment.
Jackson
Aimee L
AL
Rosetta Inpharmatics LLC, a wholly-owned subsidiary of Merck and Co., Inc., Seattle, WA 98109, USA. aimee_ jackson@merck.com
Mao
Mao
M
Kobayashi
Sumire
S
Ward
Teresa
T
Biery
Matthew
M
Dai
Hongyue
H
Bartz
Steven R
SR
Linsley
Peter S
PS