Open Access

PNA-mediated modulation and redirection of Her-2 pre-mRNA splicing: Specific skipping of erbB-2 exon 19 coding for the ATP catalytic domain

  • Authors:
    • Stanislava Pankratova
    • Birgit N. Nielsen
    • Takehiko Shiraishi
    • Peter E. Nielsen
  • View Affiliations

  • Published online on: January 1, 2010     https://doi.org/10.3892/ijo_00000472
  • Pages: 29-38
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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.

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January 2010
Volume 36 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Pankratova, S., Nielsen, B.N., Shiraishi, T., & Nielsen, P.E. (2010). PNA-mediated modulation and redirection of Her-2 pre-mRNA splicing: Specific skipping of erbB-2 exon 19 coding for the ATP catalytic domain. International Journal of Oncology, 36, 29-38. https://doi.org/10.3892/ijo_00000472
MLA
Pankratova, S., Nielsen, B. N., Shiraishi, T., Nielsen, P. E."PNA-mediated modulation and redirection of Her-2 pre-mRNA splicing: Specific skipping of erbB-2 exon 19 coding for the ATP catalytic domain". International Journal of Oncology 36.1 (2010): 29-38.
Chicago
Pankratova, S., Nielsen, B. N., Shiraishi, T., Nielsen, P. E."PNA-mediated modulation and redirection of Her-2 pre-mRNA splicing: Specific skipping of erbB-2 exon 19 coding for the ATP catalytic domain". International Journal of Oncology 36, no. 1 (2010): 29-38. https://doi.org/10.3892/ijo_00000472