ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2010
Sequence-specific targeting of IGF-I and IGF-IR genes by camptothecins.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Oligonucleotide-Recognizing Topoisomerase Inhibitors (OTIs): Precision Gene Editors for Neurodegenerative Diseases?International journal of molecular sciences · 2022Review
- The past and presence of gene targeting: from chemicals and DNA via proteins to RNA.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
- Sequence selectivity of the cleavage sites induced by topoisomerase I inhibitors: a molecular dynamics study.Nucleic acids research · 2013Article
- Regulation of transcription through light-activation and light-deactivation of triplex-forming oligonucleotides in mammalian cells.ACS chemical biology · 2012Article
- Small interfering RNA targeted to IGF-IR delays tumor growth and induces proinflammatory cytokines in a mouse breast cancer model.PloS one · 2012Article
- Replication-fork stalling and processing at a single psoralen interstrand crosslink in Xenopus egg extracts.PloS one · 2011Article
- Targeted gene correction using psoralen, chlorambucil and camptothecin conjugates of triplex forming peptide nucleic acid (PNA).Artificial DNA, PNA & XNA · 2011Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 5 countries.
Funding
Abstract
We and others have clearly demonstrated that a topoisomerase I (Top1) inhibitor, such as camptothecin (CPT), coupled to a triplex-forming oligonucleotide (TFO) through a suitable linker can be used to cause site-specific cleavage of the targeted DNA sequence in in vitro models. Here we evaluated whether these molecular tools induce sequence-specific DNA damage in a genome context. We targeted the insulin-like growth factor (IGF)-I axis and in particular promoter 1 of IGF-I and intron 2 of type 1 insulin-like growth factor receptor (IGF-IR) in cancer cells. The IGF axis molecules represent important targets for anticancer strategies, because of their central role in oncogenic maintenance and metastasis processes. We chemically attached 2 CPT derivatives to 2 TFOs. Both conjugates efficiently blocked gene expression in cells, reducing the quantity of mRNA transcribed by 70-80%, as measured by quantitative RT-PCR. We confirmed that the inhibitory mechanism of these TFO conjugates was mediated by Top1-induced cleavage through the use of RNA interference experiments and a camptothecin-resistant cell line. In addition, induction of phospho-H2AX foci supports the DNA-damaging activity of TFO-CPT conjugates at specific sites. The evaluated conjugates induce a specific DNA damage at the target gene mediated by Top1.
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Registered trials
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