| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Institute of Molecular and Cell Biology, National University of Singapore, 10 Kent Ridge Crescent, Singapore 0511, Republic of Singapore
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.
1 To whom requests for reprints should be addressed.
Received 2/21/95. Accepted 8/15/95.
This article has been cited by other articles:
|
|
 |
|
  W. Gu, J. Ding, X. Wang, R. L. de Kluyver, N. A. Saunders, I. H. Frazer, and K.-N. Zhao Generalized substitution of isoencoding codons shortens the duration of papillomavirus L1 protein expression in transiently gene-transfected keratinocytes due to cell differentiation Nucleic Acids Res., July 9, 2007; (2007) gkm496v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Gu, M. Li, W. M. Zhao, N. X. Fang, S. Bu, I. H. Frazer, and K.-N. Zhao tRNASer(CGA) differentially regulates expression of wild-type and codon-modified papillomavirus L1 genes Nucleic Acids Res., August 19, 2004; 32(15): 4448 - 4461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Chakrabarti, K. Veeraraghavalu, V. Tergaonkar, Y. Liu, E. J. Androphy, M. A. Stanley, and S. Krishna Human Papillomavirus Type 16 E6 Amino Acid 83 Variants Enhance E6-Mediated MAPK Signaling and Differentially Regulate Tumorigenesis by Notch Signaling and Oncogenic Ras J. Virol., June 1, 2004; 78(11): 5934 - 5945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-U. Bernard Established and potential strategies against papillomavirus infections J. Antimicrob. Chemother., February 1, 2004; 53(2): 137 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. z. Hausen Papillomaviruses Causing Cancer: Evasion From Host-Cell Control in Early Events in Carcinogenesis J Natl Cancer Inst, May 3, 2000; 92(9): 690 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Beerheide, H.-U. Bernard, Y.-J. Tan, A. Ganesan, W. G. Rice, and A. E. Ting Potential Drugs Against Cervical Cancer: Zinc-Ejecting Inhibitors of the Human Papillomavirus Type 16 E6 Oncoprotein J Natl Cancer Inst, July 21, 1999; 91(14): 1211 - 1220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Butz, C. Denk, A. Ullmann, M. Scheffner, and F. Hoppe-Seyler Induction of apoptosis in human papillomaviruspositive cancer cells by peptide aptamers targeting the viral E6 oncoprotein PNAS, June 6, 2000; 97(12): 6693 - 6697. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
