Human papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization
Abstract The NF-kB family of transcription factors regulates important biological functions including cell growth, survival and the immune response. We found that Human Papillomavirus type 16 (HPV-16) E7 and E6/E7 proteins inhibited basal and TNF-alpha-inducible NF-kB activity in human epithelial ce...
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| Veröffentlicht in: | Virology (New York, N.Y.) N.Y.), 2012-03, Vol.425 (1), p.53-60 |
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| container_title | Virology (New York, N.Y.) |
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| creator | Vandermark, Erik R Deluca, Krysta A Gardner, Courtney R Marker, Daniel F Schreiner, Cynthia N Strickland, David A Wilton, Katelynn M Mondal, Sumona Woodworth, Craig D |
| description | Abstract The NF-kB family of transcription factors regulates important biological functions including cell growth, survival and the immune response. We found that Human Papillomavirus type 16 (HPV-16) E7 and E6/E7 proteins inhibited basal and TNF-alpha-inducible NF-kB activity in human epithelial cells cultured from the cervical transformation zone, the anatomic region where most cervical cancers develop. In contrast, HPV-16 E6 regulated NF-kB in a cell type- and cell growth-dependent manner. NF-kB influenced immortalization of cervical cells by HPV16. Inhibition of NF-kB by an IkB alpha repressor mutant increased colony formation and immortalization by HPV-16. In contrast, activation of NF-kB by constitutive expression of p65 inhibited proliferation and immortalization. Our results suggest that inhibition of NF-kB by HPV-16 E6/E7 contributes to immortalization of cells from the cervical transformation zone. |
| doi_str_mv | 10.1016/j.virol.2011.12.023 |
| format | Article |
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We found that Human Papillomavirus type 16 (HPV-16) E7 and E6/E7 proteins inhibited basal and TNF-alpha-inducible NF-kB activity in human epithelial cells cultured from the cervical transformation zone, the anatomic region where most cervical cancers develop. In contrast, HPV-16 E6 regulated NF-kB in a cell type- and cell growth-dependent manner. NF-kB influenced immortalization of cervical cells by HPV16. Inhibition of NF-kB by an IkB alpha repressor mutant increased colony formation and immortalization by HPV-16. In contrast, activation of NF-kB by constitutive expression of p65 inhibited proliferation and immortalization. Our results suggest that inhibition of NF-kB by HPV-16 E6/E7 contributes to immortalization of cells from the cervical transformation zone.</description><identifier>ISSN: 0042-6822</identifier><identifier>EISSN: 1096-0341</identifier><identifier>DOI: 10.1016/j.virol.2011.12.023</identifier><identifier>PMID: 22284893</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; BIOLOGICAL FUNCTIONS ; CELL PROLIFERATION ; Cell Transformation, Viral ; Cells, Cultured ; Cervical cancer ; Cervix Uteri - cytology ; Cervix Uteri - metabolism ; Cervix Uteri - virology ; COLONY FORMATION ; Defensins ; Epithelial Cells - metabolism ; Epithelial Cells - virology ; EPITHELIUM ; Female ; Foreskin ; Foreskin - cytology ; Foreskin - virology ; Gene Expression Regulation ; GROWTH ; Human papillomavirus 16 ; Human papillomavirus 16 - genetics ; Human papillomavirus 16 - growth & development ; Human papillomavirus 16 - metabolism ; Human papillomavirus 16 - pathogenicity ; Humans ; Immortalization ; Infectious Disease ; INHIBITION ; Male ; MUTANTS ; NEOPLASMS ; NF-kappa B - antagonists & inhibitors ; NF-kappa B - metabolism ; NF-kB ; Oncogene Proteins, Viral - genetics ; Oncogene Proteins, Viral - metabolism ; Oral epithelium ; Papillomavirus ; Papillomavirus E7 Proteins - genetics ; Papillomavirus E7 Proteins - metabolism ; Repressor Proteins - genetics ; Repressor Proteins - metabolism ; TRANSCRIPTION FACTORS ; Transformation zone</subject><ispartof>Virology (New York, N.Y.), 2012-03, Vol.425 (1), p.53-60</ispartof><rights>Elsevier Inc.</rights><rights>2012 Elsevier Inc.</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><rights>2011 Elsevier Inc. All rights reserved 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c573t-8bbb826144c2bd5137c1a93bd9c90a49136d6ad6dd8475b174fee8c7e3efd4363</citedby><cites>FETCH-LOGICAL-c573t-8bbb826144c2bd5137c1a93bd9c90a49136d6ad6dd8475b174fee8c7e3efd4363</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0042682212000165$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22284893$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22149265$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Vandermark, Erik R</creatorcontrib><creatorcontrib>Deluca, Krysta A</creatorcontrib><creatorcontrib>Gardner, Courtney R</creatorcontrib><creatorcontrib>Marker, Daniel F</creatorcontrib><creatorcontrib>Schreiner, Cynthia N</creatorcontrib><creatorcontrib>Strickland, David A</creatorcontrib><creatorcontrib>Wilton, Katelynn M</creatorcontrib><creatorcontrib>Mondal, Sumona</creatorcontrib><creatorcontrib>Woodworth, Craig D</creatorcontrib><title>Human papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization</title><title>Virology (New York, N.Y.)</title><addtitle>Virology</addtitle><description>Abstract The NF-kB family of transcription factors regulates important biological functions including cell growth, survival and the immune response. We found that Human Papillomavirus type 16 (HPV-16) E7 and E6/E7 proteins inhibited basal and TNF-alpha-inducible NF-kB activity in human epithelial cells cultured from the cervical transformation zone, the anatomic region where most cervical cancers develop. In contrast, HPV-16 E6 regulated NF-kB in a cell type- and cell growth-dependent manner. NF-kB influenced immortalization of cervical cells by HPV16. Inhibition of NF-kB by an IkB alpha repressor mutant increased colony formation and immortalization by HPV-16. In contrast, activation of NF-kB by constitutive expression of p65 inhibited proliferation and immortalization. Our results suggest that inhibition of NF-kB by HPV-16 E6/E7 contributes to immortalization of cells from the cervical transformation zone.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>BIOLOGICAL FUNCTIONS</subject><subject>CELL PROLIFERATION</subject><subject>Cell Transformation, Viral</subject><subject>Cells, Cultured</subject><subject>Cervical cancer</subject><subject>Cervix Uteri - cytology</subject><subject>Cervix Uteri - metabolism</subject><subject>Cervix Uteri - virology</subject><subject>COLONY FORMATION</subject><subject>Defensins</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - virology</subject><subject>EPITHELIUM</subject><subject>Female</subject><subject>Foreskin</subject><subject>Foreskin - cytology</subject><subject>Foreskin - virology</subject><subject>Gene Expression Regulation</subject><subject>GROWTH</subject><subject>Human papillomavirus 16</subject><subject>Human papillomavirus 16 - genetics</subject><subject>Human papillomavirus 16 - growth & development</subject><subject>Human papillomavirus 16 - metabolism</subject><subject>Human papillomavirus 16 - pathogenicity</subject><subject>Humans</subject><subject>Immortalization</subject><subject>Infectious Disease</subject><subject>INHIBITION</subject><subject>Male</subject><subject>MUTANTS</subject><subject>NEOPLASMS</subject><subject>NF-kappa B - antagonists & inhibitors</subject><subject>NF-kappa B - metabolism</subject><subject>NF-kB</subject><subject>Oncogene Proteins, Viral - genetics</subject><subject>Oncogene Proteins, Viral - metabolism</subject><subject>Oral epithelium</subject><subject>Papillomavirus</subject><subject>Papillomavirus E7 Proteins - genetics</subject><subject>Papillomavirus E7 Proteins - metabolism</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - metabolism</subject><subject>TRANSCRIPTION FACTORS</subject><subject>Transformation zone</subject><issn>0042-6822</issn><issn>1096-0341</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1uEzEUhUcIREPhCZCQJRasJvhv_hZUgiqlSBUsgLXlsW8apx57sD1B4XV4UTxJqIANK9vyd46v7z1F8ZzgJcGkfr1d7kzwdkkxIUtCl5iyB8WC4K4uMePkYbHAmNOybik9K57EuMX53DT4cXFGKW1527FF8fN6GqRDoxyNtX6Q2XKKKO1HQKRGqxpJp9EKNWgMPoFxEUmbIKCPV-XdO2QcUpNNUwCNFISdUdIiGE3agDV5q8DaeLAwbmN6k4x3yK9P6mw5ZNN4wNBt8N_T5ggPgw9JWvNDzoqnxaO1tBGendbz4uvV6svldXnz6f2Hy7c3paoalsq27_uW1oRzRXtdEdYoIjvW6051WPKOsFrXUtdat7ypetLwNUCrGmCw1pzV7Ly4OPqOUz-AVuBSkFaMwQwy7IWXRvx948xG3PqdYLTtqgpng5dHAx-TEVGZBGqjvHOgkqCU8I7WVaZenZ4J_tsEMYnBxLkF0oGfoshQ2xLMu0yyI6mCjzHA-r4WgsWcAbEVhwyIOQOCUJEzkFUv_vzGveb30DPw5ghAbubOQJhLBadAmzBXqr35zwMX_-iVNW6e_R3sIW79FFyekyAiZoH4PMdwTiGhOYEkd-AXl0rbZg</recordid><startdate>20120330</startdate><enddate>20120330</enddate><creator>Vandermark, Erik R</creator><creator>Deluca, Krysta A</creator><creator>Gardner, Courtney R</creator><creator>Marker, Daniel F</creator><creator>Schreiner, Cynthia N</creator><creator>Strickland, David A</creator><creator>Wilton, Katelynn M</creator><creator>Mondal, Sumona</creator><creator>Woodworth, Craig D</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><scope>5PM</scope></search><sort><creationdate>20120330</creationdate><title>Human papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization</title><author>Vandermark, Erik R ; Deluca, Krysta A ; Gardner, Courtney R ; Marker, Daniel F ; Schreiner, Cynthia N ; Strickland, David A ; Wilton, Katelynn M ; Mondal, Sumona ; Woodworth, Craig D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c573t-8bbb826144c2bd5137c1a93bd9c90a49136d6ad6dd8475b174fee8c7e3efd4363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>BIOLOGICAL FUNCTIONS</topic><topic>CELL PROLIFERATION</topic><topic>Cell Transformation, Viral</topic><topic>Cells, Cultured</topic><topic>Cervical cancer</topic><topic>Cervix Uteri - cytology</topic><topic>Cervix Uteri - metabolism</topic><topic>Cervix Uteri - virology</topic><topic>COLONY FORMATION</topic><topic>Defensins</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial Cells - virology</topic><topic>EPITHELIUM</topic><topic>Female</topic><topic>Foreskin</topic><topic>Foreskin - cytology</topic><topic>Foreskin - virology</topic><topic>Gene Expression Regulation</topic><topic>GROWTH</topic><topic>Human papillomavirus 16</topic><topic>Human papillomavirus 16 - genetics</topic><topic>Human papillomavirus 16 - growth & development</topic><topic>Human papillomavirus 16 - metabolism</topic><topic>Human papillomavirus 16 - pathogenicity</topic><topic>Humans</topic><topic>Immortalization</topic><topic>Infectious Disease</topic><topic>INHIBITION</topic><topic>Male</topic><topic>MUTANTS</topic><topic>NEOPLASMS</topic><topic>NF-kappa B - antagonists & inhibitors</topic><topic>NF-kappa B - metabolism</topic><topic>NF-kB</topic><topic>Oncogene Proteins, Viral - genetics</topic><topic>Oncogene Proteins, Viral - metabolism</topic><topic>Oral epithelium</topic><topic>Papillomavirus</topic><topic>Papillomavirus E7 Proteins - genetics</topic><topic>Papillomavirus E7 Proteins - metabolism</topic><topic>Repressor Proteins - genetics</topic><topic>Repressor Proteins - metabolism</topic><topic>TRANSCRIPTION FACTORS</topic><topic>Transformation zone</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vandermark, Erik R</creatorcontrib><creatorcontrib>Deluca, Krysta A</creatorcontrib><creatorcontrib>Gardner, Courtney R</creatorcontrib><creatorcontrib>Marker, Daniel F</creatorcontrib><creatorcontrib>Schreiner, Cynthia N</creatorcontrib><creatorcontrib>Strickland, David A</creatorcontrib><creatorcontrib>Wilton, Katelynn M</creatorcontrib><creatorcontrib>Mondal, Sumona</creatorcontrib><creatorcontrib>Woodworth, Craig D</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Virology (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vandermark, Erik R</au><au>Deluca, Krysta A</au><au>Gardner, Courtney R</au><au>Marker, Daniel F</au><au>Schreiner, Cynthia N</au><au>Strickland, David A</au><au>Wilton, Katelynn M</au><au>Mondal, Sumona</au><au>Woodworth, Craig D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization</atitle><jtitle>Virology (New York, N.Y.)</jtitle><addtitle>Virology</addtitle><date>2012-03-30</date><risdate>2012</risdate><volume>425</volume><issue>1</issue><spage>53</spage><epage>60</epage><pages>53-60</pages><issn>0042-6822</issn><eissn>1096-0341</eissn><abstract>Abstract The NF-kB family of transcription factors regulates important biological functions including cell growth, survival and the immune response. 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| identifier | ISSN: 0042-6822 |
| ispartof | Virology (New York, N.Y.), 2012-03, Vol.425 (1), p.53-60 |
| issn | 0042-6822 1096-0341 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals; EZB Electronic Journals Library |
| subjects | 60 APPLIED LIFE SCIENCES BIOLOGICAL FUNCTIONS CELL PROLIFERATION Cell Transformation, Viral Cells, Cultured Cervical cancer Cervix Uteri - cytology Cervix Uteri - metabolism Cervix Uteri - virology COLONY FORMATION Defensins Epithelial Cells - metabolism Epithelial Cells - virology EPITHELIUM Female Foreskin Foreskin - cytology Foreskin - virology Gene Expression Regulation GROWTH Human papillomavirus 16 Human papillomavirus 16 - genetics Human papillomavirus 16 - growth & development Human papillomavirus 16 - metabolism Human papillomavirus 16 - pathogenicity Humans Immortalization Infectious Disease INHIBITION Male MUTANTS NEOPLASMS NF-kappa B - antagonists & inhibitors NF-kappa B - metabolism NF-kB Oncogene Proteins, Viral - genetics Oncogene Proteins, Viral - metabolism Oral epithelium Papillomavirus Papillomavirus E7 Proteins - genetics Papillomavirus E7 Proteins - metabolism Repressor Proteins - genetics Repressor Proteins - metabolism TRANSCRIPTION FACTORS Transformation zone |
| title | Human papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization |
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