Abstract:
: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.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Pankratova S,Nielsen BN,Shiraishi T,Nielsen PEsubject
Has Abstractpub_date
2010-01-01 00:00:00pages
29-38issue
1eissn
1019-6439issn
1791-2423journal_volume
36pub_type
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