Gene expression changes in a tumor xenograft by a pyrrole-imidazole polyamide.
Proc Natl Acad Sci U S A, 2012/10/02;109(40):16041-5.
Raskatov JA[1], Nickols NG, Hargrove AE, Marinov GK, Wold B, Dervan PB
Affiliations
PMID: 22988074DOI: 10.1073/pnas.1214267109
Impact factor: 12.779
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.
MeSH terms
Cell Line, Tumor; DNA; Fluorescein-5-isothiocyanate; Gene Expression Regulation, Neoplastic; High-Throughput Nucleotide Sequencing; Humans; Imidazoles; Microscopy, Confocal; Molecular Structure; Nylons; Pyrroles; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, RNA; Solid-Phase Synthesis Techniques; Transplantation, Heterologous
More resources
Full text:
Europe PubMed Central; PubMed Central
EndNote: Download