title: Gene expression changes in a tumor xenograft by a pyrrole-imidazole polyamide.
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.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Jevgenij A
authors.initials: JA
authors.lastname: Raskatov
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Nickols
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Hargrove
authors.forename: Georgi K
authors.initials: GK
authors.lastname: Marinov
authors.forename: Barbara
authors.initials: B
authors.lastname: Wold
authors.forename: Peter B
authors.initials: PB
authors.lastname: Dervan
mesh_terms: D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000502:physiology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D018613:Microscopy, Confocal; D015394:Molecular Structure; D009757:Nylons / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D060327:Solid-Phase Synthesis Techniques; D014183:Transplantation, Heterologous
chemical_list: D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles; D004247:DNA; D016650:Fluorescein-5-isothiocyanate