Gene expression changes in a tumor xenograft by a pyrrole-imidazole polyamide.
- Authors
- Type
- Published Article
- Journal
- Proceedings of the National Academy of Sciences
- Publisher
- Proceedings of the National Academy of Sciences
- Volume
- 109
- Issue
- 40
- Identifiers
- DOI: 10.1073/pnas.1214267109
- Source
- UCSC Aging biomedical-ucsc
- License
- Unknown
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.