PNA-mediated modulation and redirection of Her-2 pre-mRNA splicing: specific skipping of erbB-2 exon 19 coding for the ATP catalytic domain
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The Her-2 receptor coded for by the proto-oncogenic erbB-2 gene is a clinically validated target for treatment of a significant genetic subclass of breast cancers, and Her-2 is also overexpressed or mutated in a range of other cancers. In an approach to exploit antisense mediated splicing interference as a means of manipulating erbB-2 expression in a therapeutically relevant fashion, we have studied the effect on mRNA splicing of a series of peptide nucleic acid (PNA) oligomers targeting specific intron-exon junctions in the erbB-2 pre-mRNA. In particular, we are interested in identifying PNA oligomers that specifically induce skipping of exon 19 as this exon is coding for the ATP catalytic domain of Her-2, and if expressed such truncated version of the Her-2 protein should be functionally inactive in a dominant negative fashion. Therefore, antisense compounds having efficient erbB-2 exon 19 skipping activity could be very interesting in terms of drug discovery. In the present study we identified PNA oligomers having such activity in SK-BR-3 and HeLa cancer cells in culture.
Original language | English |
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Journal | International Journal of Oncology |
Volume | 36 |
Issue number | 1 |
Pages (from-to) | 29-38 |
Number of pages | 9 |
ISSN | 1019-6439 |
DOIs | |
Publication status | Published - Jan 2010 |
ID: 16863233