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  Nuclear proto-oncogene products transactivate the human papillomavirus type 16 promoter.

Nürnberg, W., Artuc, M., Vorbrüggen, G., Kalkbrenner, F., Mölling, K., Czarnetzki, B. M., et al. (1995). Nuclear proto-oncogene products transactivate the human papillomavirus type 16 promoter. British Journal of Cancer, 71(5), 1018-1024. doi:10.1038/bjc.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-295D-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-295E-5
Genre: Journal Article

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Nürnberg, W., Author
Artuc, M., Author
Vorbrüggen, G.1, Author              
Kalkbrenner, F., Author
Mölling, K., Author
Czarnetzki, B. M., Author
Schadendorf, D., Author
Affiliations:
1Research Group of Molecular Cell Dynamics, MPI for biophysical chemistry, Max Planck Society, ou_578593              

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 Abstract: Human papillomavirus (HPV) type 16 and 18 viral genomes are frequently detected in cervical and penile cancer biopsies. Although this strongly suggests a prominent role for HPV infection in the development of genital cancer, other genetic or environmental factors are also involved. Genital cancer is postulated to result from loss of cellular control functions, which leads to an unregulated expression of HPV oncogenic proteins. In our study, we determined the trans-activating properties of nuclear proto-oncogene proteins c-Fos, c-Jun and c-Myc on P97 enhancer/promoter activity of HPV16. Using a CAT-reporter construct containing the HPV16 enhancer/promoter element, we investigated the trans-activating effects of c-Fos, c-Jun, c-Myc, and E2 in cervical HT-3 cells. c-Fos and c-Jun overexpression resulted in a 3.3- and 3.1-fold up-regulation of CAT activity. Only 2-fold induction was determined by co-transfection with c-myc and the viral transcription factor E2. Based on these findings, we investigated the expression of HPV DNA (16 and 18) as well as nuclear proto-oncogenes (c-fos, c-jun and c-myc) in nine cervical cancers by in situ hybridisation. In six out of nine carcinomas, HPV16 and/or HPV18 DNA was detectable. All tumours showed an intense and homogeneous expression of c-fos and c-jun mRNA, while the signal for c-myc was detectable only in four specimens. These data suggest that deregulation of nuclear proto-oncogene expression may contribute to an overexpression of HPV-derived oncogenic proteins (E6 and E7), which is generally hypothesised to be an important step in the malignant transformation of HPV-associated tumours.

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Language(s): eng - English
 Dates: 1995-05
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1038/bjc
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Title: British Journal of Cancer
Source Genre: Journal
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Pages: - Volume / Issue: 71 (5) Sequence Number: - Start / End Page: 1018 - 1024 Identifier: -