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Spotlight on Molecular Profiling

MicroRNA expression profiles for the NCI-60 cancer cell panel

¹ Program of Pharmacogenomics, Department of Pharmacology and the Comprehensive Cancer Center, College of Medicine, Departments of ² Statistics, ³ Mathematical Biosciences Institute, and ⁴ Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio; ⁵ Genomics and Bioinformatics Group, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland; ⁶ GeneLogic, Inc., Gaithersburg, Maryland

Requests for reprints: Paul Blower, Department of Pharmacology, The Ohio State University, 5072 Graves Hall, 333 West 10th Avenue, Columbus, OH 43210. Phone: 614-688-5565; Fax: 614-292-7232. E-mail: blower.7{at}osu.edu

Abstract

Advances in the understanding of cancer cell biology and response to drug treatment have benefited from new molecular technologies and methods for integrating information from multiple sources. The NCI-60, a panel of 60 diverse human cancer cell lines, has been used by the National Cancer Institute to screen >100,000 chemical compounds and natural product extracts for anticancer activity. The NCI-60 has also been profiled for mRNA and protein expression, mutational status, chromosomal aberrations, and DNA copy number, generating an unparalleled public resource for integrated chemogenomic studies. Recently, microRNAs have been shown to target particular sets of mRNAs, thereby preventing translation or accelerating mRNA turnover. To complement the existing NCI-60 data sets, we have measured expression levels of microRNAs in the NCI-60 and incorporated the resulting data into the CellMiner program package for integrative analysis. Cell line groupings based on microRNA expression were generally consistent with tissue type and with cell line clustering based on mRNA expression. However, mRNA expression seemed to be somewhat more informative for discriminating among tissue types than was microRNA expression. In addition, we found that there does not seem to be a significant correlation between microRNA expression patterns and those of known target transcripts. Comparison of microRNA expression patterns and compound potency patterns showed significant correlations, suggesting that microRNAs may play a role in chemoresistance. Combined with gene expression and other biological data using multivariate analysis, microRNA expression profiles may provide a critical link for understanding mechanisms involved in chemosensitivity and chemoresistance. [Mol Cancer Ther 2007;6(5):1483–91]

Grant support: National Institute of General Medical Sciences grant GM61390; NSF Agreement no. 0112050; and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

⁷ http://dtp.nci.nih.gov/docs/cancer/cancer_data.html

⁸ http://discover.nci.nih.gov

⁹ http://dtp.nci.nih.gov

¹⁰ Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

Received 1/ 4/07; revised 3/13/07; accepted 3/23/07.

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