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Identification of human papillomavirus type 18 transforming genes in immortalized and primary cells
Abstract
The selective retention and expression of the E6-E7 region of human papillomavirus (HPV) types 16 and 18 in cervical carcinomas suggests that these viral sequences play a role in the development of genital neoplasia. Each of three possible gene products, E6, E6*, and E7, from this region of HPV-18 were examined for transforming properties in several types of rodent cells. We have found that in immortalized fibroblasts, both E6 and E7 (but not E6*) are capable of inducing anchorage-independent growth. In rat embryo cells, the HPV-18 E7 open reading frame was an effective immortalizing agent and complemented an activated ras oncogene for transformation. In both immortalized and primary cells, transformation was observed when the HPV-18 sequences were expressed from either the HPV-18 promoter or a heterologous promoter. The E6-E7 region is not, however, the sole transforming domain of HPV-18, since another portion of the early region, possibly E5, also exhibited transforming capability in immortalized fibroblasts. The development of human cervical carcinomas may therefore involve a series of steps involving multiple viral and cellular gene products.
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“subsequently, E7 was recognized as the major transforming protein of high-risk HPVs, using mutational analyses in transformation assays [52,79,80,81,82,83,84]”
From The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis (2021) · cites this paper as [79]
In the citing paper
“HPV-16 E6/E7-expressing cell lines were immortalized but were not tumourigenic in nude mice, although they could induce tumours after several passages or in cooperation with additional oncogenes such as ras or fos [79,90,91,92]”
From The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis (2021) · cites this paper as [79]
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Research works printed but not linked: 6
- [14]14. Durst, M., L. Gissman, H. Ikenberg, and H. zur Hausen. 1983. A papillomavirus DNÀ from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc. Natl. Acad. Sci. USA 80:3812–3815.
- [21]21. Haslinger, A., and M. Karin. 1985. Upstream promoter element of the human metallothionein-IIA gene can act like an enhancer element. Proc. Natl. Acad. Sci. USA 82:8572–8576.
- [33]33. Schiller, J. T., W. C. Vass, and D. R. Lowy. 1984. Identification of a second transforming region in bovine papillomavirus DNA. Proc. Natl. Acad. Sci. USA 81:7880–7884.
- [37]37. Smotkin, D., and F. O. Wettstein. 1986. Transcription of human papillomavirus type 16 early genes in a cervical cancer and a cancer-derived cell line and identification of the E7 protein. Proc. Natl. Acad. Sci. USA 83:4680–4684.
- [40]40. Tsunkokawa, Y., N. Takebe, T. Kasamatsu, M. Terada, and T. Sugimura. 1986. Transforming activity of human papillomavirus type 16 DNA sequences in a cervical cancer. Proc. Natl. Acad. Sci. USA 83:2200–2203.
- [42]42. Yang, Y.-C., H. Okayama, and P. M. Howley. 1985. Bovine papillomavirus contains multiple transforming genes. Proc. Natl. Acad. Sci. USA 82:1030–1034.
Cited by
The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53
Scheffner, M., Werness, B. A., Huibregtse, J. M., Levine, A. J., & Howley, P. M. (1990) · Cell · doi:10.1016/0092-8674(90)90409-8 · Cited by 3,995
Basukala, O., & Banks, L. (2021) · Viruses · doi:10.3390/v13101892 · Cited by 137
Metadata
- Authors
- Bedell, M. A., Jones, K. H., Grossman, S. R., & Laimins, L. A.
- Affiliations
- Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 1989-03
- Volume
- 63
- Issue
- 3
- Pages
- 1247-1255
- ISSN
- 0022-538X
- 1098-5514
- Cited by
- 129
- References
- 0
- Language
- en
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- Bedell, M. A., Jones, K. H., Grossman, S. R., & Laimins, L. A. (1989). Identification of human papillomavirus type 18 transforming genes in immortalized and primary cells. Journal of Virology. https://doi.org/10.1128/jvi.63.3.1247-1255.1989
