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Series GSE7969

Query DataSets for GSE7969

Status

Public on Jan 01, 2008

Title

Chromosome 20q amplification regulates in vitro response to Kinesin-5 inhibitor

Organism

Homo sapiens

Experiment type

Expression profiling by array

Summary

We identified gene expression signatures predicting responsiveness to a Kinesin-5 (kinesin spindle protein, 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 overexpression of AURKA, TPX2 and MYBL2 is functionally involved in resistance to Kinesin-5i. Furthermore, our results suggest that patients whose tumors overexpress AURKA due to amplifications of 20q will be more likely to resist treatment with Kinesin-5 inhibitor, and that inactivation of AURKA may sensitize these patients to treatment.
Keywords: Cell line comparison

Overall design

A series of colon cancer cell lines was analyzed for gene expression signatures. These gene expression signatures were then correlated with in vitro responsiveness of each cell line to a KSP inhibitor (Kinesin-5i). Transcripts whose expression was correlated with response (>0.5 or <-0.5) were identified as reporters of cellular response to this inhibitor. Reporters were further tested by RNAi for functional role in response to this inhibitor.

Contributor(s)

Jackson AL, Mao M, Kobayashi S, Ward T, Biery M, Dai H, Bartz SR, Linsley PS

Citation(s)

19259408

Submission date

May 31, 2007

Last update date

Mar 17, 2012

Contact name

Aimee Jackson

Organization name

Regulus Therapeutics