Cited by 283

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siRNA targeting of the viral E6 oncogene efficiently kills human papillomavirus-positive cancer cells

Butz, Karin, Ristriani, Tutik, Hengstermann, Arnd, Denk, Claudia, Scheffner, Martin, Hoppe-Seyler, Felix·2003·Oncogene

Abstract

The targeted inhibition of antiapoptotic factors in tumour cells may provide a rational approach towards the development of novel anticancer therapies. Using human papillomavirus (HPV)-transformed cells as a model system, we investigated if RNA interference (RNAi)-mediated gene silencing can be employed in order to overcome the apoptosis resistance of cancer cells. We found that both vector-borne and synthetic small interfering (si)RNAs, specifically directed against the antiapoptotic HPV E6 oncogene, restored dormant tumour suppressor pathways in HPV-positive cancer cells that are otherwise inactive in the presence of E6. This ultimately resulted in massive apoptotic cell death, selectively in HPV-positive tumour cells. These findings show that RNAi provides a powerful molecular strategy to inactivate intracellular E6 function efficiently. Moreover, they define E6 as a most promising therapeutic target to eliminate HPV-positive tumour cells specifically by RNAi. Thus, by sequence-specific targeting of antiapoptotic genes, siRNAs may be developed into novel therapeutics that can efficiently correct the apoptosis deficiency of cancer cells.

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Crossref · 10.1038/sj.onc.1206894

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Cited by

Metadata

Authors
Butz, K., Ristriani, T., Hengstermann, A., Denk, C., Scheffner, M., & Hoppe-Seyler, F.
Venue
Oncogene
Published
2003-09-04
Volume
22
Issue
38
Pages
5938-5945
ISSN
  • 0950-9232
  • 1476-5594
Cited by
283
References
2
Language
en

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