@ARTICLE{Richard20103435,
author={Richard, C. and Lanner, C. and Naryzhny, S.N. and Sherman, L. and Lee, H. and Lambert, P.F. and Zehbe, I.},
title={The immortalizing and transforming ability of two common human papillomavirus 16 E6 variants with different prevalences in cervical cancer},
journal={Oncogene},
year={2010},
volume={29},
number={23},
pages={3435-3445},
doi={10.1038/onc.2010.93},
note={cited By 44},
url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-77953479092&doi=10.1038%2fonc.2010.93&partnerID=40&md5=a2b7b7205b3c0b34e3f9617c09aeccaa},
affiliation={Research Laboratory, Thunder Bay Regional Health Sciences Centre, Thunder Bay, ON, Canada; Molecular Genetics, Northern Ontario School of Medicine, Laurentian University, Sudbury, ON, Canada; Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON, Canada; Northeastern Ontario Regional Cancer Program, Sudbury Regional Hospital, Sudbury, ON, Canada; Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, United States; Probe Development and Biomarker Exploration, Thunder Bay Regional Research Institute, 980 Oliver Road, Thunder Bay, ON P7B 6V4, Canada},
abstract={Persistent infection with high-risk human papillomaviruses (HPVs), especially type 16 has been undeniably linked to cervical cancer. The Asian-American (AA) variant of HPV16 is more common in the Americas than the prototype in cervical cancer. The different prevalence is based on three amino acid changes within the E6 protein denoted Q14H/H78Y/L83V. To investigate the mechanism(s) behind this observation, both E6 proteins, in the presence of E7, were evaluated for their ability to extend the life span of and transform primary human foreskin keratinocytes (PHFKs). Long-term cell culture studies resulted in death at passage 9 of vector-transduced PHFKs (negative control), but survival of both E6 PHFKs to passage 65 (and beyond). Compared with E6/E7 PHFKs, AA/E7 PHFKs were significantly faster dividing, developed larger cells in monolayer cultures, showed double the epithelial thickness and expressed cytokeratin 10 when grown as organotypic raft cultures. Telomerase activation and p53 inactivation, two hallmarks of immortalization, were not significantly different between the two populations. Both were resistant to anoikis at later passages, but only AA/E7 PHFKs acquired the capacity for in vitro transformation. Proteomic analysis revealed markedly different protein patterns between E6/E7 and AA/E7, particularly with respect to key cellular metabolic enzymes. Our results provide new insights into the reasons underlying the greater prevalence of the AA variant in cervical cancer as evidenced by characteristics associated with higher oncogenic potential. © 2010 Macmillan Publishers Limited All rights reserved.},
author_keywords={Cervical cancer;  Human papillomavirus;  Human primary foreskin keratinocytes;  Immortalization;  Transformation},
}

{"_id":"Kx3QDtAgRJ8mbDoiF","bibbaseid":"richard-lanner-naryzhny-sherman-lee-lambert-zehbe-theimmortalizingandtransformingabilityoftwocommonhumanpapillomavirus16e6variantswithdifferentprevalencesincervicalcancer-2010","author_short":["Richard, C.","Lanner, C.","Naryzhny, S.","Sherman, L.","Lee, H.","Lambert, P.","Zehbe, I."],"bibdata":{"bibtype":"article","type":"article","author":[{"propositions":[],"lastnames":["Richard"],"firstnames":["C."],"suffixes":[]},{"propositions":[],"lastnames":["Lanner"],"firstnames":["C."],"suffixes":[]},{"propositions":[],"lastnames":["Naryzhny"],"firstnames":["S.N."],"suffixes":[]},{"propositions":[],"lastnames":["Sherman"],"firstnames":["L."],"suffixes":[]},{"propositions":[],"lastnames":["Lee"],"firstnames":["H."],"suffixes":[]},{"propositions":[],"lastnames":["Lambert"],"firstnames":["P.F."],"suffixes":[]},{"propositions":[],"lastnames":["Zehbe"],"firstnames":["I."],"suffixes":[]}],"title":"The immortalizing and transforming ability of two common human papillomavirus 16 E6 variants with different prevalences in cervical cancer","journal":"Oncogene","year":"2010","volume":"29","number":"23","pages":"3435-3445","doi":"10.1038/onc.2010.93","note":"cited By 44","url":"https://www.scopus.com/inward/record.uri?eid=2-s2.0-77953479092&doi=10.1038%2fonc.2010.93&partnerID=40&md5=a2b7b7205b3c0b34e3f9617c09aeccaa","affiliation":"Research Laboratory, Thunder Bay Regional Health Sciences Centre, Thunder Bay, ON, Canada; Molecular Genetics, Northern Ontario School of Medicine, Laurentian University, Sudbury, ON, Canada; Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON, Canada; Northeastern Ontario Regional Cancer Program, Sudbury Regional Hospital, Sudbury, ON, Canada; Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, United States; Probe Development and Biomarker Exploration, Thunder Bay Regional Research Institute, 980 Oliver Road, Thunder Bay, ON P7B 6V4, Canada","abstract":"Persistent infection with high-risk human papillomaviruses (HPVs), especially type 16 has been undeniably linked to cervical cancer. The Asian-American (AA) variant of HPV16 is more common in the Americas than the prototype in cervical cancer. The different prevalence is based on three amino acid changes within the E6 protein denoted Q14H/H78Y/L83V. To investigate the mechanism(s) behind this observation, both E6 proteins, in the presence of E7, were evaluated for their ability to extend the life span of and transform primary human foreskin keratinocytes (PHFKs). Long-term cell culture studies resulted in death at passage 9 of vector-transduced PHFKs (negative control), but survival of both E6 PHFKs to passage 65 (and beyond). Compared with E6/E7 PHFKs, AA/E7 PHFKs were significantly faster dividing, developed larger cells in monolayer cultures, showed double the epithelial thickness and expressed cytokeratin 10 when grown as organotypic raft cultures. Telomerase activation and p53 inactivation, two hallmarks of immortalization, were not significantly different between the two populations. Both were resistant to anoikis at later passages, but only AA/E7 PHFKs acquired the capacity for in vitro transformation. Proteomic analysis revealed markedly different protein patterns between E6/E7 and AA/E7, particularly with respect to key cellular metabolic enzymes. Our results provide new insights into the reasons underlying the greater prevalence of the AA variant in cervical cancer as evidenced by characteristics associated with higher oncogenic potential. © 2010 Macmillan Publishers Limited All rights reserved.","author_keywords":"Cervical cancer; Human papillomavirus; Human primary foreskin keratinocytes; Immortalization; Transformation","bibtex":"@ARTICLE{Richard20103435,\r\nauthor={Richard, C. and Lanner, C. and Naryzhny, S.N. and Sherman, L. and Lee, H. and Lambert, P.F. and Zehbe, I.},\r\ntitle={The immortalizing and transforming ability of two common human papillomavirus 16 E6 variants with different prevalences in cervical cancer},\r\njournal={Oncogene},\r\nyear={2010},\r\nvolume={29},\r\nnumber={23},\r\npages={3435-3445},\r\ndoi={10.1038/onc.2010.93},\r\nnote={cited By 44},\r\nurl={https://www.scopus.com/inward/record.uri?eid=2-s2.0-77953479092&doi=10.1038%2fonc.2010.93&partnerID=40&md5=a2b7b7205b3c0b34e3f9617c09aeccaa},\r\naffiliation={Research Laboratory, Thunder Bay Regional Health Sciences Centre, Thunder Bay, ON, Canada; Molecular Genetics, Northern Ontario School of Medicine, Laurentian University, Sudbury, ON, Canada; Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON, Canada; Northeastern Ontario Regional Cancer Program, Sudbury Regional Hospital, Sudbury, ON, Canada; Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, United States; Probe Development and Biomarker Exploration, Thunder Bay Regional Research Institute, 980 Oliver Road, Thunder Bay, ON P7B 6V4, Canada},\r\nabstract={Persistent infection with high-risk human papillomaviruses (HPVs), especially type 16 has been undeniably linked to cervical cancer. The Asian-American (AA) variant of HPV16 is more common in the Americas than the prototype in cervical cancer. The different prevalence is based on three amino acid changes within the E6 protein denoted Q14H/H78Y/L83V. To investigate the mechanism(s) behind this observation, both E6 proteins, in the presence of E7, were evaluated for their ability to extend the life span of and transform primary human foreskin keratinocytes (PHFKs). Long-term cell culture studies resulted in death at passage 9 of vector-transduced PHFKs (negative control), but survival of both E6 PHFKs to passage 65 (and beyond). Compared with E6/E7 PHFKs, AA/E7 PHFKs were significantly faster dividing, developed larger cells in monolayer cultures, showed double the epithelial thickness and expressed cytokeratin 10 when grown as organotypic raft cultures. Telomerase activation and p53 inactivation, two hallmarks of immortalization, were not significantly different between the two populations. Both were resistant to anoikis at later passages, but only AA/E7 PHFKs acquired the capacity for in vitro transformation. Proteomic analysis revealed markedly different protein patterns between E6/E7 and AA/E7, particularly with respect to key cellular metabolic enzymes. Our results provide new insights into the reasons underlying the greater prevalence of the AA variant in cervical cancer as evidenced by characteristics associated with higher oncogenic potential. © 2010 Macmillan Publishers Limited All rights reserved.},\r\nauthor_keywords={Cervical cancer; Human papillomavirus; Human primary foreskin keratinocytes; Immortalization; Transformation},\r\n}","author_short":["Richard, C.","Lanner, C.","Naryzhny, S.","Sherman, L.","Lee, H.","Lambert, P.","Zehbe, I."],"key":"Richard20103435","id":"Richard20103435","bibbaseid":"richard-lanner-naryzhny-sherman-lee-lambert-zehbe-theimmortalizingandtransformingabilityoftwocommonhumanpapillomavirus16e6variantswithdifferentprevalencesincervicalcancer-2010","role":"author","urls":{"Paper":"https://www.scopus.com/inward/record.uri?eid=2-s2.0-77953479092&doi=10.1038%2fonc.2010.93&partnerID=40&md5=a2b7b7205b3c0b34e3f9617c09aeccaa"},"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://bio.pnpi.nrcki.ru/wp-content/uploads/2019/12/lpro_2019_10.txt","dataSources":["eoAALb5LHAEShrPHa"],"keywords":[],"search_terms":["immortalizing","transforming","ability","two","common","human","papillomavirus","variants","different","prevalences","cervical","cancer","richard","lanner","naryzhny","sherman","lee","lambert","zehbe"],"title":"The immortalizing and transforming ability of two common human papillomavirus 16 E6 variants with different prevalences in cervical cancer","year":2010}