Induction of apoptosis in cervical carcinoma cells by peptide aptamers that bind to the HPV-16 E7 oncoprotein.
Human papillomaviruses (HPV) of the high-risk type are causally involved in human tumors, in particular cervical carcinoma. Expression of the viral oncogenes E6 and E7 is maintained in HPV-positive tumors, and it was shown that E6 and E7 of HPV-16 can immortalize human keratinocytes, the natural host cells of the virus. Expression of the viral genes is also required for maintenance of the transformed phenotype. The oncogenic activity of the E6 and E7 oncoproteins is mediated by their physical and functional interaction with cellular regulatory proteins. To knock out the function of the E7 protein in living cells, we have developed peptide aptamers with high specific binding activity for the E7 protein of HPV-16. We show here that E7-binding peptide aptamers induce programmed cell death (apoptosis) in E7-expressing cells, whereas E7-negative cells are not affected. Furthermore, E7-binding peptide aptamers induce apoptosis in HPV-16-positive tumor cells derived from cervical carcinoma. The data suggest that E7-binding peptide aptamers may be useful tools to specifically eliminate HPV-positive tumors.
Nauenburg
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S
Institut f. Biomedizinische Alternsforschung der Osterreichischen Akademie der Wissenschaften, Rennweg 10, A-6020 Innsbruck, Austria.
Zwerschke
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W
Jansen-Durr
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P
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D005260:Female; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008954:Models, Biological; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D019151:Peptide Library; D010455:Peptides; D011993:Recombinant Fusion Proteins; C059731:oncogene protein E7, Human papillomavirus type 16