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,...
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Veröffentlicht in: | Virology (New York, N.Y.) N.Y.), 2014-11, Vol.468, p.647-659 |
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creator | Shterzer, Naama Heyman, Dariya Shapiro, Beny Yaniv, Abraham Jackman, Anna Serour, Francis Chaouat, Malka Gonen, Pinhas Tommasino, Massimo Sherman, Levana |
description | 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. |
doi_str_mv | 10.1016/j.virol.2014.09.015 |
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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.</description><identifier>ISSN: 0042-6822</identifier><identifier>EISSN: 1096-0341</identifier><identifier>DOI: 10.1016/j.virol.2014.09.015</identifier><identifier>PMID: 25443667</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Animals ; APOPTOSIS ; Bak ; Bax ; Beta HPVs ; CALCIUM ; CARCINOGENS ; CELL PROLIFERATION ; Cell Survival - radiation effects ; Cell Transformation, Viral - physiology ; COMPARATIVE EVALUATIONS ; Cutaneous HPV types ; EPITHELIOMAS ; Gene Expression Regulation, Viral ; Human papillomavirus ; Human papillomavirus 16 ; Humans ; Infectious Disease ; Keratinocytes - radiation effects ; Keratinocytes - virology ; LIFE SPAN ; Mice ; NIH 3T3 Cells ; p53 ; Papillomaviridae - classification ; Papillomaviridae - genetics ; Papillomaviridae - metabolism ; Plasmids ; PROTEINS ; SIGNALS ; SKIN ; Skin cancer ; Skin Neoplasms - virology ; Ultraviolet Rays ; UVB ; Viral Proteins - genetics ; Viral Proteins - metabolism ; Warts ; Warts - virology</subject><ispartof>Virology (New York, N.Y.), 2014-11, Vol.468, p.647-659</ispartof><rights>Elsevier Inc.</rights><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. 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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.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Animals</subject><subject>APOPTOSIS</subject><subject>Bak</subject><subject>Bax</subject><subject>Beta HPVs</subject><subject>CALCIUM</subject><subject>CARCINOGENS</subject><subject>CELL PROLIFERATION</subject><subject>Cell Survival - radiation effects</subject><subject>Cell Transformation, Viral - physiology</subject><subject>COMPARATIVE EVALUATIONS</subject><subject>Cutaneous HPV types</subject><subject>EPITHELIOMAS</subject><subject>Gene Expression Regulation, Viral</subject><subject>Human papillomavirus</subject><subject>Human papillomavirus 16</subject><subject>Humans</subject><subject>Infectious Disease</subject><subject>Keratinocytes - radiation effects</subject><subject>Keratinocytes - virology</subject><subject>LIFE SPAN</subject><subject>Mice</subject><subject>NIH 3T3 Cells</subject><subject>p53</subject><subject>Papillomaviridae - classification</subject><subject>Papillomaviridae - genetics</subject><subject>Papillomaviridae - metabolism</subject><subject>Plasmids</subject><subject>PROTEINS</subject><subject>SIGNALS</subject><subject>SKIN</subject><subject>Skin cancer</subject><subject>Skin Neoplasms - virology</subject><subject>Ultraviolet Rays</subject><subject>UVB</subject><subject>Viral Proteins - genetics</subject><subject>Viral Proteins - metabolism</subject><subject>Warts</subject><subject>Warts - virology</subject><issn>0042-6822</issn><issn>1096-0341</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUsFu1DAQjRCIbgtfgIQsceGyi-04cXwAqVSFIlXiAOVqOc6E9W5iB9tZtP_FBzLpFg5cuHjG8nszz_OmKF4wumGU1W92m4OLYdhwysSGqg1l1aNixaiq17QU7HGxolTwdd1wflacp7SjeJeSPi3OeCVEWddyVfy6mUfjyWQmNwxhNFhyTiQfJ0ikgww2Q0ecJ2mPx08TcyLGd8QabyGSzvU9BnzKW3CR5Gh86kMcnf9OphgmiNlhpXbOxIZxDH44YjL7DNHYTO6-vUdyN1tsgvClnTsAiZCm4BMSsfL2XuAeCdn5YI8Z0rPiSW-GBM8f4kVx9-H669XN-vbzx09Xl7drW3Ga1w0Xpu24klUjoAVrcDaqNm1ZC9v3hnem4qVqbU-BG9k2jTKSi75R0gohVVVeFK9OdUPKTifrUODWBu9Rp-ZclBWVNaJen1D4gx8zpKxHlywMg_EQ5qRZXVNBJacKoeUJamNIKUKvp-hGE4-aUb2Yqnf63lS9mKqp0mgqsl4-NJjbEbq_nD8uIuDtCQA4jIODuGgFdKhzcZHaBfefBu_-4dvBeWfNsIcjpF2Yo8c5a6YT11R_WfZqWSsmlkyq8jeHF84j</recordid><startdate>20141101</startdate><enddate>20141101</enddate><creator>Shterzer, Naama</creator><creator>Heyman, Dariya</creator><creator>Shapiro, Beny</creator><creator>Yaniv, Abraham</creator><creator>Jackman, Anna</creator><creator>Serour, Francis</creator><creator>Chaouat, Malka</creator><creator>Gonen, Pinhas</creator><creator>Tommasino, Massimo</creator><creator>Sherman, Levana</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U9</scope><scope>H94</scope><scope>OTOTI</scope></search><sort><creationdate>20141101</creationdate><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</title><author>Shterzer, Naama ; 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subjects | 60 APPLIED LIFE SCIENCES Animals APOPTOSIS Bak Bax Beta HPVs CALCIUM CARCINOGENS CELL PROLIFERATION Cell Survival - radiation effects Cell Transformation, Viral - physiology COMPARATIVE EVALUATIONS Cutaneous HPV types EPITHELIOMAS Gene Expression Regulation, Viral Human papillomavirus Human papillomavirus 16 Humans Infectious Disease Keratinocytes - radiation effects Keratinocytes - virology LIFE SPAN Mice NIH 3T3 Cells p53 Papillomaviridae - classification Papillomaviridae - genetics Papillomaviridae - metabolism Plasmids PROTEINS SIGNALS SKIN Skin cancer Skin Neoplasms - virology Ultraviolet Rays UVB Viral Proteins - genetics Viral Proteins - metabolism Warts Warts - virology |
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 |
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