In vitro and in vivo inhibition of human papillomavirus type 16 E6 and E7 genes - PubMed (original) (raw)
. 1995 Oct 15;55(20):4599-605.
Affiliations
- PMID: 7553636
In vitro and in vivo inhibition of human papillomavirus type 16 E6 and E7 genes
T M Tan et al. Cancer Res. 1995.
Abstract
Human cervical cancers are often associated with human papillomavirus (HPV). In HPV-positive cervical cancers, the oncoproteins E6 and E7 are consistently expressed. In this study, the effects of antisense inhibition of both proteins were examined. Phosphorothioate oligonucleotides (ODNs) AE6 and AE7 complementary to regions flanking the start codons of HPV16 E6 and E7 genes, respectively, were synthesized. These anti-HPV ODNs inhibited the growth of cervical cell lines CaSki and SiHa, which harbor HPV16 but had little effect on cells that do not. Both ODNs also affected the ability of CaSki cells to form colonies in soft agar. In nude mice, treatment with either AE6, AE7, or a mixture of both led to substantially smaller tumors. AE7 was observed to inhibit E7 synthesis. The AE6 ODN probably exerts its effect by suppressing the expression of E6 as well as E7. Cell cultures and tumors treated with AE6 showed a decrease in E7 expression. In addition, an antisense ODN targeted at the retinoblastoma gene was able to reverse some of the inhibitory effect of AE6 on CaSki cells, indicating that AE6 inhibited E7 synthesis. This study further demonstrates that anti-HPV ODNs may be useful therapeutically.
Similar articles
- In vitro antigene therapy targeting HPV-16 E6 and E7 in cervical carcinoma.
Madrigal M, Janicek MF, Sevin BU, Perras J, Estape R, Peñalver M, Averette HE. Madrigal M, et al. Gynecol Oncol. 1997 Jan;64(1):18-25. doi: 10.1006/gyno.1996.4515. Gynecol Oncol. 1997. PMID: 8995542 - Retrovirus-mediated delivery of HPV16 E7 antisense RNA inhibited tumorigenicity of CaSki cells.
Choo CK, Ling MT, Suen CK, Chan KW, Kwong YL. Choo CK, et al. Gynecol Oncol. 2000 Sep;78(3 Pt 1):293-301. doi: 10.1006/gyno.2000.5916. Gynecol Oncol. 2000. PMID: 10985883 - Advances in the development of ribozymes and antisense oligodeoxynucleotides as antiviral agents for human papillomaviruses.
Alvarez-Salas LM, Benítez-Hess ML, DiPaolo JA. Alvarez-Salas LM, et al. Antivir Ther. 2003 Aug;8(4):265-78. Antivir Ther. 2003. PMID: 14518695 Review. - [Biological significance of HPV sequences integrated into cancer cells].
Tsunokawa Y. Tsunokawa Y. Gan To Kagaku Ryoho. 1989 Mar;16(3 Pt 2):562-8. Gan To Kagaku Ryoho. 1989. PMID: 2539785 Review. Japanese.
Cited by
- Papillomavirus genome structure, expression, and post-transcriptional regulation.
Zheng ZM, Baker CC. Zheng ZM, et al. Front Biosci. 2006 Sep 1;11:2286-302. doi: 10.2741/1971. Front Biosci. 2006. PMID: 16720315 Free PMC article. Review. - Generalized substitution of isoencoding codons shortens the duration of papillomavirus L1 protein expression in transiently gene-transfected keratinocytes due to cell differentiation.
Gu W, Ding J, Wang X, de Kluyver RL, Saunders NA, Frazer IH, Zhao KN. Gu W, et al. Nucleic Acids Res. 2007;35(14):4820-32. doi: 10.1093/nar/gkm496. Epub 2007 Jul 9. Nucleic Acids Res. 2007. PMID: 17621583 Free PMC article. - Targeting the human papillomavirus E6 and E7 oncogenes through expression of the bovine papillomavirus type 1 E2 protein stimulates cellular motility.
Morrison MA, Morreale RJ, Akunuru S, Kofron M, Zheng Y, Wells SI. Morrison MA, et al. J Virol. 2011 Oct;85(20):10487-98. doi: 10.1128/JVI.05126-11. Epub 2011 Aug 10. J Virol. 2011. PMID: 21835799 Free PMC article. - Human papillomavirus in the setting of immunodeficiency: Pathogenesis and the emergence of next-generation therapies to reduce the high associated cancer risk.
Hewavisenti RV, Arena J, Ahlenstiel CL, Sasson SC. Hewavisenti RV, et al. Front Immunol. 2023 Mar 7;14:1112513. doi: 10.3389/fimmu.2023.1112513. eCollection 2023. Front Immunol. 2023. PMID: 36960048 Free PMC article. Review. - Antisense inhibition of virus infections.
Kilkuskie RE, Field AK. Kilkuskie RE, et al. Adv Pharmacol. 1997;40:437-83. doi: 10.1016/s1054-3589(08)60147-7. Adv Pharmacol. 1997. PMID: 9217933 Free PMC article. Review.