Spontaneous tumour development in human papillomavirus type 8 E6 transgenic mice and rapid induction by UV-light exposure and wounding.
Cutaneous human papillomavirus type 8 (HPV8) is carcinogenic in patients with epidermodysplasia verruciformis. Transgenic mice with the complete early region (CER) of HPV8 spontaneously developed papillomas, dysplasia and squamous cell carcinomas of the skin. To characterize the role of individual early genes in carcinogenesis, the E6 and E6/E7 genes were expressed separately in transgenic mice. Nearly all HPV8-E6-positive mice spontaneously developed multifocal tumours, characterized by papillomatosis, hyperkeratosis and varying degrees of epidermal dysplasia. In 6 % of the cases, the tumours became malignant, comparable with HPV8-CER mice. Thus, in the murine epidermis, E6 is the major oncogene necessary and sufficient to induce spontaneous tumour development up to the level of squamous cell carcinoma. To evaluate the synergistic effects of UV light and wound healing, the skin of HPV8 mice was irradiated with UVA/UVB light or wounded with punch biopsies. These treatments induced papillomatosis in HPV8-CER and -E6 mice within 3 weeks. Irradiation with UVA alone did not induce papillomatosis and UVB alone had a weaker effect than UVA/UVB, indicating a synergistic role of UVA in UVB-induced papillomatosis. An HPV8 infection persisting over decades in interaction with sun burns and wound healing processes may be a relevant cause of skin cancer in humans.
Marcuzzi
Gian Paolo
GP
Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.|Institute of Virology, University of Cologne, 50935 Cologne, Germany.
Hufbauer
Martin
M
Institute of Virology, University of Cologne, 50935 Cologne, Germany.
Kasper
Hans Udo
HU
Department of Pathology, University of Cologne, 50924 Cologne, Germany.
Weißenborn
Sönke Jan
SJ
Institute of Virology, University of Cologne, 50935 Cologne, Germany.
Smola
Sigrun
S
Institute of Virology, Saarland University, 66421 Homburg/Saar, Germany.|Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
Pfister
Herbert
H
Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.|Institute of Virology, University of Cologne, 50935 Cologne, Germany.
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000503:physiopathology / Q000821:virology; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D015967:Gene Expression Regulation, Viral; D006801:Humans; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000209:etiology* / Q000503:physiopathology / Q000821:virology; D013997:Time Factors; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014950:Wounds, Penetrating / Q000150:complications*
C466081:E6 protein, Human papillomavirus type 8; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins