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

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2003

Autor:innen

Butz, Karin
Ristriani, Tutik
Hengstermann, Arnd
Denk, Claudia
Hoppe-Seyler, Felix

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Published

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Oncogene. 2003, 22(38), pp. 5938-5945. ISSN 0950-9232. eISSN 1476-5594. Available under: doi: 10.1038/sj.onc.1206894

Zusammenfassung

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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Fachgebiet (DDC)
570 Biowissenschaften, Biologie

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RNA interference; human papillomavirus; apoptosis; tumour virus; tumour therapy

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ISO 690BUTZ, Karin, Tutik RISTRIANI, Arnd HENGSTERMANN, Claudia DENK, Martin SCHEFFNER, Felix HOPPE-SEYLER, 2003. siRNA targeting of the viral E6 oncogene efficiently kills human papillomavirus-positive cancer cells. In: Oncogene. 2003, 22(38), pp. 5938-5945. ISSN 0950-9232. eISSN 1476-5594. Available under: doi: 10.1038/sj.onc.1206894
BibTex
@article{Butz2003-09-04siRNA-42200,
  year={2003},
  doi={10.1038/sj.onc.1206894},
  title={siRNA targeting of the viral E6 oncogene efficiently kills human papillomavirus-positive cancer cells},
  number={38},
  volume={22},
  issn={0950-9232},
  journal={Oncogene},
  pages={5938--5945},
  author={Butz, Karin and Ristriani, Tutik and Hengstermann, Arnd and Denk, Claudia and Scheffner, Martin and Hoppe-Seyler, Felix}
}
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