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Journal of Virology, May 2004, p. 4797-4805, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4797-4805.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Increased Incidence of Squamous Cell Carcinomas in Mastomys natalensis Papillomavirus E6 Transgenic Mice during Two-Stage Skin Carcinogenesis

Iris Helfrich,* Min Chen,{dagger} Rainer Schmidt, Gerhard Fürstenberger, Annette Kopp-Schneider, David Trick, Hermann-Josef Gröne, Harald zur Hausen, and Frank Rösl

Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany

Received 7 August 2003/ Accepted 23 December 2003

Papillomaviruses cause certain forms of human cancers, most notably carcinomas of the uterine cervix. In contrast to the well-established involvement of papillomavirus infection in the etiology of cervical carcinomas and in carcinomas of a rare hereditary condition, epidermodysplasia verruciformis, a causative role for cutaneous human papillomavirus types in the development of nonmelanoma skin cancer has not been proven. In order to better understand the functions of individual genes of cutaneous papillomavirus types, we generated transgenic mice carrying oncogene E6 of the Mastomys natalensis papillomavirus (MnPV), which causes keratoacanthomas of the skin in its natural host. In the present study, we demonstrate that under conditions of experimental two-stage skin carcinogenesis, fast-paced squamous cell carcinomas develop in nearly 100% of MnPV E6 transgenic mice in comparison to 10% in their nontransgenic littermates (log rank test; P < 0.0001). Therefore, we conclude that the MnPV E6 transgene favors the malignant progression of chemically induced tumors. Whereas an activating H-ras mutation is a consistent feature in benign and malignant tumors in wild-type mice, the majority of papillomas and keratoacanthomas and all squamous cell carcinomas obtained in MnPV E6 transgenic mice contain nonmutated ras alleles. These results indicate that the development of squamous cell carcinomas in MnPV E6 transgenic mice does not depend on an activated H-ras oncogene.

* Corresponding author. Mailing address: Forschungsschwerpunkt Angewandte Tumorvirologie, Abteilung Virale Transformationsmechanismen, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. Phone: 496221/424919. Fax: 496221/424902. E-mail: i.helfrich{at}dkfz.de.

{dagger} Present address: Texas Heart Institute, Houston, TX 77303.

Journal of Virology, May 2004, p. 4797-4805, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4797-4805.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nafz, J., Kohler, A., Ohnesorge, M., Nindl, I., Stockfleth, E., Rosl, F. (2007). Persistence of Mastomys natalensis papillomavirus in multiple organs identifies novel targets for infection. J. Gen. Virol. 88: 2670-2678 [Abstract] [Full Text]  
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