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RNA effective against brain cancer
© BioMed Central Ltd 2002
- Published: 19 August 2002
- Epidermal Growth Factor Receptor
- Brain Cancer
- Dependent Protein Kinase
- Truncated Form
- Cell Implantation
Double-stranded RNA (dsRNA)-dependent protein kinase PKR is a growth inhibitory protein that induces death in virally infected cells, but its potential in controlling tumor growth is unknown. In August 19 Nature Biotechnology, Alexei Shir and Alexander Levitzki at The Hebrew University of Jerusalem show that activating PKR with a dsRNA molecule can be an effective method of inhibiting murine glioma growth (Nat Biotechnol 2002, DOI:10.1038/nbt730).
Shir & Levitzki used the U87MGΔEGFR cell line that expresses a truncated form of epidermal growth factor receptor (EGFR) - Δ(2-7) EGFR. They observed that expression of a 39-nucleotide (nt) AS RNA complementary to the unique exon 1 to 8 junction activated PKR and caused selective death of cells harboring the truncated EGFR, both in vitro and in vivo but did not affect cells expressing wild-type EGFR. In addition, they showed that a lentiviral vector expressing the 39-nt AS sequence activated PKR and strongly inhibited glioblastoma growth in mouse brain when injected after tumor cell implantation.
This PKR-mediated killing strategy may be useful in treating many patients with cancers that express a unique RNA species, suggest the authors.