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Journal of Virology, November 2006, p. 11153-11164, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.00954-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

E6/E7 Expression of Human Papillomavirus Type 20 (HPV-20) and HPV-27 Influences Proliferation and Differentiation of the Skin in UV-Irradiated SKH-hr1 Transgenic Mice

Angelika Michel,¹ Annette Kopp-Schneider,² Hanswalter Zentgraf,³ Achim D. Gruber,⁴ and Ethel-Michele de Villiers^1*

Division for the Characterization of Tumorviruses, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany,¹ Central Unit Biostatistics, Deutsches Krebsforschungszentrum, Heidelberg, Germany,² Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany,³ Department of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany⁴

Received 10 May 2006/ Accepted 1 September 2006

The functional role of UV irradiation, in combination with the E6 and E7 proteins of the cutaneous human papillomavirus (HPV) types in the malignant conversion of benign papillomatous lesions, has not been elucidated. Transgenic SKH-hr1 hairless mice expressing HPV-20 and HPV-27 E6 and E7 proteins in the suprabasal compartment were generated and exposed to chronic UV irradiation. Histological and immunohistochemical examination of skin samples revealed enhanced proliferation of the epidermal layers and papilloma formation in both transgenic strains in comparison to what was observed with nontransgenic mice. Squamous cell carcinoma developed in the HPV-20 E6/E7 transgenic line as well as in the HPV-27 E6/E7 transgenic line. Several weeks after cessation of UV-B exposure, enhanced proliferation, as measured by BrdU incorporation, was maintained only in HPV-20 transgenic skin. Keratin 6 expression was increased in the transgenic mice throughout all cell layers. Expression of the differentiation markers involucrin and loricrin was reduced and disturbed. p63 expression was differentially regulated with high levels of cytoplasmic expression in clusters of cells in the granular layer of the skin in the transgenic lines 20 weeks after cessation of UV-B exposure, in contrast to uninterrupted staining in the nontransgenic lines. p53 was expressed in clusters of cells in nontransgenic and HPV-27 transgenic mice, in contrast to an even distribution in a higher number of cells in HPV-20 transgenic animals.

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* Corresponding author. Mailing address: Division for the Characterization of Tumorviruses, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany. Phone: 49-6221-424655. Fax: 49-6221-424822. E-mail: e.devilliers{at}dkfz.de.

Published ahead of print on 13 September 2006.

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Journal of Virology, November 2006, p. 11153-11164, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.00954-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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