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Gene expression changes in a tumor xenograft by a pyrrole-imidazole polyamide

Raskatov, Jevgenij A. and Nickols, Nicholas G. and Hargrove, Amanda E. and Marinov, Georgi K. and Wold, Barbara and Dervan, Peter B. (2012) Gene expression changes in a tumor xenograft by a pyrrole-imidazole polyamide. Proceedings of the National Academy of Sciences of the United States of America, 109 (40). pp. 16041-16045. ISSN 0027-8424. PMCID PMC3479560. doi:10.1073/pnas.1214267109. https://resolver.caltech.edu/CaltechAUTHORS:20121106-105719691

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Abstract

Gene regulation by DNA binding small molecules could have important therapeutic applications. This study reports the investigation of a DNA-binding pyrrole-imidazole polyamide targeted to bind the DNA sequence 5′-WGGWWW-3′ with reference to its potency in a subcutaneous xenograft tumor model. The molecule is capable of trafficking to the tumor site following subcutaneous injection and modulates transcription of select genes in vivo. An FITC-labeled analogue of this polyamide can be detected in tumor-derived cells by confocal microscopy. RNA deep sequencing (RNA-seq) of tumor tissue allowed the identification of further affected genes, a representative panel of which was interrogated by quantitative reverse transcription-PCR and correlated with cell culture expression levels.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.1214267109 DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479560/PubMed CentralArticle
http://www.pnas.org/content/109/40/16041/suppl/DCSupplementalPublisherSupporting Information
ORCID:
AuthorORCID
Marinov, Georgi K.0000-0003-1822-7273
Wold, Barbara0000-0003-3235-8130
Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 2012 National Academy of Sciences. Freely available online through the PNAS open access option. Contributed by Peter B. Dervan, August 20, 2012 (sent for review July 10, 2012). Published online before print September 17, 2012. J.A.R. is grateful to the Alexander von Humboldt foundation for the award of a Feodor Lynen postdoctoral fellowship. We thank Michael J. Waring for careful editing of the manuscript. N.G.N. would like to acknowledge the National Institutes of Health (NIH) and the Jonsson Cancer Center Foundation (JCCF) at UCLA for postdoctoral support. A.E.H. thanks the California Tobacco-Related Disease Research Program (19FT-0105) and the NIH (NRSA 1F32CA156833) for postdoctoral support. Sequencing was conducted at the Millard and Muriel Jacobs Genetics and Genomics Laboratory at California Institute of Technology. We are grateful for support by The Ellison Medical Foundation (AG-SS-2256-09) and the National Institutes of Health (GM051747). Author contributions: J.A.R., and P.B.D. designed research; J.A.R., N.G.N., and A.E.H. performed research; J.A.R., N.G.N., A.E.H., G.K.M., B.W., and P.B.D. analyzed data; and J.A.R., and P.B.D. wrote the paper. The authors declare no conflict of interest. Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE40218). This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1214267109/-/DCSupplemental.
Funders:
Funding AgencyGrant Number
Alexander von Humboldt FoundationUNSPECIFIED
UCLA Jonsson Cancer Center FoundationUNSPECIFIED
California Tobacco-Related Disease Research Program19FT-0105
NIH Postdoctoral Fellowship1F32CA156833
Ellison Medical FoundationAG-SS-2256-09
NIHGM-051747
Subject Keywords:tumor RNA-sequencing; eXpress; in vivo circulation; efficacy
Issue or Number:40
PubMed Central ID:PMC3479560
DOI:10.1073/pnas.1214267109
Record Number:CaltechAUTHORS:20121106-105719691
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20121106-105719691
Official Citation:Jevgenij A. Raskatov, Nicholas G. Nickols, Amanda E. Hargrove, Georgi K. Marinov, Barbara Wold, and Peter B. Dervan Gene expression changes in a tumor xenograft by a pyrrole-imidazole polyamide PNAS 2012 109 (40) 16041-16045; published ahead of print September 17, 2012, doi:10.1073/pnas.1214267109
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:35304
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:06 Nov 2012 22:42
Last Modified:09 Nov 2021 23:14

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