The human papillomavirus type 8 E2 protein induces skin tumors in transgenic mice.
Transgenic mice expressing early genes of the cutaneous human papillomavirus 8 (HPV8) spontaneously develop skin papillomas, epidermal dysplasia, and squamous cell carcinoma (6%). As the HPV8 protein E2 revealed transforming capacity in vitro, we generated three epidermal specific HPV8-E2-transgenic FVB/N mouse lines to dissect its role in tumor development. The rate of tumor formation in the three lines correlated with the different E2-mRNA levels. More than 60% of heterozygous line 2 mice, but none of the HPV8-negative littermates, spontaneously developed ulcerous lesions of the skin over an observation period of up to 144 weeks, beginning on average 74+/-22 weeks after birth. Most lesions presented infundibular hyperplasia and acanthosis combined with low-grade dysplasia. Severe dysplasia of the epidermis occurred in 6%. Two carcinomas revealed a sharply demarcated spindle-cell component. Only 3 weeks after a single UV irradiation, 87% of heterozygous line 2 and 36% of line 35 mice developed skin tumors. A rapidly growing invasive tumor composed of spindle cells arose 10 weeks after irradiation of a line-35 animal. The histology of skin cancers in HPV8-E2 mice is reminiscent of a subset of highly aggressive squamous cell carcinoma in immunosuppressed transplant recipients with a massive spindle-cell component.
Pfefferle
Regina
R
Institute of Virology, Center for Molecular Medicine, University of Cologne, Cologne, Germany.
Marcuzzi
Gian Paolo
GP
Akgül
Baki
B
Kasper
Hans Udo
HU
Schulze
Falko
F
Haase
Ingo
I
Wickenhauser
Claudia
C
Pfister
Herbert
H
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000503:physiopathology / Q000821:virology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000528:radiation effects; D004195:Disease Models, Animal; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D005814:Genes, Viral / Q000502:physiology; D006801:Humans; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009381:Neoplasms, Radiation-Induced / Q000235:genetics; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000502:physiology*; D010212:Papilloma / Q000235:genetics / Q000503:physiopathology / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000150:complications; D012867:Skin / Q000473:pathology / Q000528:radiation effects / Q000821:virology; D012878:Skin Neoplasms / Q000235:genetics / Q000503:physiopathology* / Q000821:virology*; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D014466:Ultraviolet Rays / Q000009:adverse effects
D009856:Oncogene Proteins, Viral; D015534:Trans-Activators; C468298:oncogene protein E2, Human papillomavirus type 8