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We previously showed that the beta HPV type 38 E6 and E7 oncoproteins are able to inactivate the tumor suppressors p53 and retinoblastoma. Here, both viral proteins were expressed in primary human skin keratinocytes in order to study their effects on the telomere\/telomerase system. We show that immortalization of skin keratinocytes induced by HPV38 E6\/E7 is associated with\n                    <jats:italic>hTERT<\/jats:italic>\n                    gene overexpression. This event is, in part, explained by the accumulation of the p53\u2010related protein, \u2206Np73. Despite elevated levels of\n                    <jats:italic>hTERT<\/jats:italic>\n                    mRNA, the telomerase activity detected in HPV38 E6\/E7 keratinocytes was lower than that observed in HPV16 E6\/E7 keratinocytes. The low telomerase activation in highly proliferative HPV38 E6\/E7 keratinocytes resulted in the presence of extremely short and unstable telomeres. In addition, we observed anaphase bridges, mitotic multipolarity, and dramatic genomic aberrations. Interestingly, the ectopic expression of\n                    <jats:italic>hTERT<\/jats:italic>\n                    prevents both telomere erosion and genomic instability. Thus, we showed that in HPV38 E6\/E7 keratinocytes characterized by unscheduled proliferation, suboptimal activation of telomerase and subsequent extensive telomere shortening result in genomic instability facilitating cellular immortalization. Gabet, A.\u2010S., Accardi, R., Bellopede, A., Popp, S., Boukamp, P., Sylla, B. S., Londo\u00f1o\u2010Vallejo, J. A., Tommasino, M. Impairment of the telomere\/telomerase system and genomic instability are associated with keratinocyte immortalization induced by the skin human papillomavirus type 38.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    22, 622\u2013632 (2008)\n                  <\/jats:p>","DOI":"10.1096\/fj.07-8389com","type":"journal-article","created":{"date-parts":[[2007,9,26]],"date-time":"2007-09-26T20:48:32Z","timestamp":1190839712000},"page":"622-632","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Impairment of the telomere\/telomerase system and genomic instability are associated with keratinocyte immortalization induced by the skin human papillomavirus type 38"],"prefix":"10.1096","volume":"22","author":[{"given":"Anne-Sophie","family":"Gabet","sequence":"first","affiliation":[{"name":"International Agency for Research on Cancer Lyon France"}]},{"given":"Rosita","family":"Accardi","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer Lyon France"}]},{"given":"Angelica","family":"Bellopede","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer Lyon France"}]},{"given":"Susanne","family":"Popp","sequence":"additional","affiliation":[{"name":"Deutsches Krebsforschungszentrum Heidelberg Germany"}]},{"given":"Petra","family":"Boukamp","sequence":"additional","affiliation":[{"name":"Deutsches Krebsforschungszentrum Heidelberg Germany"}]},{"given":"Bakary S.","family":"Sylla","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer Lyon France"}]},{"given":"J. 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