The E6 and E7 proteins of the cutaneous human papillomavirus type 38 display transforming properties.
Several studies have suggested the involvement of cutaneous human papillomaviruses (HPVs) in the development of nonmelanoma skin cancers. Here we have characterized the in vitro properties of E7 proteins of three cutaneous HPV types, 10, 20, and 38, which are frequently detected in skin specimens. We show that HPV38 E7 is able to inactivate the tumor suppressor pRb and induces loss of G(1)/S transition control, a key event in carcinogenesis. In contrast, HPV10 and HPV20 E7 proteins do not display these in vitro transforming activities. We also show that the two early proteins E6 and E7 of HPV38 are sufficient to corrupt the cell cycle and senescence programs in primary cells, inducing active and long-lasting proliferation of primary human keratinocytes, the natural host cells. Our study shows that E6 and E7 of this cutaneous HPV type have transforming activity in primary human cells, suggesting a role for HPV38 infection in skin carcinogenesis. In further support of such a role, we detected HPV38 DNA in approximately 50% of nonmelanoma skin cancers, but only in 10% of healthy skin specimens (P < 0.001).
Caldeira
Sandra
S
Angewandte Tumorvirologie. Genetik der Hautcarcinogenese, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany. Istituto di Dermatologia, Facoltà di Medicina, Università di Bari, Bari, Italy.
Zehbe
Ingeborg
I
Accardi
Rosita
R
Malanchi
Ilaria
I
Dong
Wen
W
Giarrè
Marianna
M
de Villiers
Ethel-Michele
EM
Filotico
Raffaele
R
Boukamp
Petra
P
Tommasino
Massimo
M
D016475:3T3 Cells; D000818:Animals; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic; D016922:Cellular Senescence; D004279:DNA, Viral / Q000032:analysis; D006801:Humans; D015603:Keratinocytes / Q000821:virology; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D027383:Papillomaviridae / Q000472:pathogenicity*; D012867:Skin / Q000821:virology; D012878:Skin Neoplasms / Q000209:etiology / Q000821:virology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; D016159:Tumor Suppressor Protein p53; C062495:oncogene protein E7, Human papillomavirus type 6