Journal article
Amplicon-dependent CCNE1 expression is critical for clonogenic survival after cisplatin treatment and is correlated with 20q11 gain in ovarian cancer
D Etemadmoghadam, J George, PA Cowin, C Cullinane, M Kansara, KL Gorringe, GK Smyth, DDL Bowtell
Plos One | PUBLIC LIBRARY SCIENCE | Published : 2010
Abstract
Genomic amplification of 19q12 occurs in several cancer types including ovarian cancer where it is associated with primary treatment failure. We systematically attenuated expression of genes within the minimally defined 19q12 region in ovarian cell lines using short-interfering RNAs (siRNA) to identify driver oncogene(s) within the amplicon. Knockdown of CCNE1 resulted in G1/S phase arrest, reduced cell viability and apoptosis only in amplification-carrying cells. Although CCNE1 knockdown increased cisplatin resistance in short-term assays, clonogenic survival was inhibited after treatment. Gain of 20q11 was highly correlated with 19q12 amplification and spanned a 2.5 Mb region including TPX..
View full abstractGrants
Awarded by National Health and Medical Research Council
Funding Acknowledgements
This study was funded by a National Health and Medical Research Council (NHMRC) project grant 628779 (www.nhmrc.gov.au). The Australian Ovarian Cancer Study is supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, The Cancer Council Victoria, Queensland Cancer Fund, The Cancer Council New South Wales, The Cancer Council South Australia, The Cancer Foundation of Western Australia, The Cancer Council Tasmania and the NHMRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.