title: Human papillomavirus types detected in skin warts and cancer differ in their transforming properties but commonly counteract UVB induced protective responses in human keratinocytes.
abstract: In the present study, E6E7 and E6 proteins of human papillomaviruses (HPVs) associated with skin warts and cancer were compared for their transforming and carcinogenic abilities in primary human keratinocytes (PHKs). We show that E6E7 of cancer associated beta HPV types, notably 49 and 24, were able to extend the life span and enhance the clonogenic efficiency of PHKs when maintained in serum free/low calcium medium. Activities of the beta HPV E6E7 were lower than those of HPV16 E6E7. In contrast, E6 proteins from HPV types detected in skin warts or cancer, notably 10, 49 and 38, attenuated UVB induced protective responses in PHKs including cell death, proliferation arrest and accumulation of the proapoptotic proteins, p53, bax or bak. Together, this investigation revealed functional differences and commonalities between HPVs associated with skin warts and cancer, and allowed the identification of specific properties of beta HPVs supporting their involvement in skin carcinogenesis.
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Naama
authors.initials: N
authors.lastname: Shterzer
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Dariya
authors.initials: D
authors.lastname: Heyman
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Beny
authors.initials: B
authors.lastname: Shapiro
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Yaniv
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Jackman
authors.affiliation: Department of Pediatric Surgery, The E. Wolfson Medical Center, Holon, Israel.
authors.forename: Francis
authors.initials: F
authors.lastname: Serour
authors.affiliation: Laboratory of Experimental Surgery, Hadassah University Hospital, Ein Karem, Jerusalem, Israel.
authors.forename: Malka
authors.initials: M
authors.lastname: Chaouat
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Pinhas
authors.initials: P
authors.lastname: Gonen
authors.affiliation: International Agency for Research on Cancer, World Health Organization, Lyon, France.
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Levana
authors.initials: L
authors.lastname: Sherman
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000528:radiation effects; D002472:Cell Transformation, Viral / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D006801:Humans; D015603:Keratinocytes / Q000528:radiation effects* / Q000821:virology*; D051379:Mice; D041681:NIH 3T3 Cells; D027383:Papillomaviridae / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D010957:Plasmids; D012878:Skin Neoplasms / Q000821:virology*; D014466:Ultraviolet Rays; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014860:Warts / Q000821:virology*
chemical_list: D014764:Viral Proteins
keywords: Apoptosis; Bak; Bax; Beta HPVs; Cutaneous HPV types; Skin; Skin cancer; UVB; Warts; p53