This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fluiter, K. Articles by Baas, F. Search for Related Content PubMed PubMed Citation Articles by Fluiter, K. Articles by Baas, F.

Tumor Genotype-specific Growth Inhibition in Vivo by Antisense Oligonucleotides against a Polymorphic Site of the Large Subunit of Human RNA Polymerase II¹

Neurozintuigen Laboratory, Academical Medical Center, 1105 AZ [K. F., A. L. M. A. t. A., M. v. G., M. N., F. B.], and Laser Center, Academical Medical Center, 1100 DE [M. C. G. A.] Amsterdam, the Netherlands

Loss of heterozygosity (LOH) reduces genes to hemizygosity in cancer cells and presents an absolute difference between normal and cancer cells. The regions of LOH are usually much larger than the tumor suppressor gene, which is lost, and are expected to contain genes that are essential for cell survival. Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation in man, often giving rise to two or more allelic forms of most genes. SNPs of essential genes that are frequently affected by LOH can be used as a target for a novel therapy against cancer cells with LOH. The SNPs can be targeted by antisense oligonucleotides (ODNs) that will discriminate between two alleles. We have designed allele-specific phosphorothioate ODNs against the gene of the large subunit of RNA polymerase II (POLR2A), a gene located in close proximity to the tumor suppressor gene p53, which frequently shows LOH in cancer cells. This report shows that phosphorothioate antisense ODNs directed against POLR2A can inhibit tumor growth in vivo as efficiently as a well-described antitumor antisense ODN directed against Ha-ras. In addition, we show that a single bp mismatch can be sufficient to obtain allele-specific inhibition of tumor growth, demonstrating that the effects observed are true antisense effects.

This article has been cited by other articles:

				O. R. Mook, F. Baas, M. B. de Wissel, and K. Fluiter Evaluation of locked nucleic acid-modified small interfering RNA in vitro and in vivo Mol. Cancer Ther., March 1, 2007; 6(3): 833 - 843. [Abstract] [Full Text] [PDF]

				K. Fluiter, A. L. M. A. ten Asbroek, M. B. de Wissel, M. E. Jakobs, M. Wissenbach, H. Olsson, O. Olsen, H. Oerum, and F. Baas In vivo tumor growth inhibition and biodistribution studies of locked nucleic acid (LNA) antisense oligonucleotides Nucleic Acids Res., February 1, 2003; 31(3): 953 - 962. [Abstract] [Full Text] [PDF]