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Melphalan reduced the levels of RNA polymerase II and cellular transcription factor Sp1 that were associated with HPV16 DNA. The resulting inhibition of transcription caused a rapid loss of the HPV16 early mRNAs encoding E6 and E7 as a result of their inherent instability. As a consequence of HPV16 E6 and E7 down\u2010regulation, the DNA damage inflicted on the cells by melphalan caused induction of p53 and activation of apoptosis in the HN26 cells. The BARD1\u2010negative phenotype of the HN26 cells may have contributed to the failure to repair DNA damage caused by melphalan, as well as to the efficient apoptosis induction. Finally, nude mice carrying the HPV16 positive tonsillar cancer cells responded better to melphalan than to cisplatin, the chemotherapeutic drug of choice for tonsillar cancer. We concluded that the short half\u2010life of the HPV16 E6 and E7 mRNAs renders HPV16\u2010driven tonsillar cancer cells particularly sensitive to DNA damaging agents such as melphalan since melphalan both inhibits transcription and causes DNA damage.<\/jats:p>","DOI":"10.1002\/ijc.31918","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T16:58:14Z","timestamp":1539190694000},"page":"297-310","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Short half\u2010life of HPV16 E6 and E7 mRNAs sensitizes HPV16\u2010positive tonsillar cancer cell line HN26 to DNA\u2010damaging drugs"],"prefix":"10.1002","volume":"144","author":[{"given":"Chengjun","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Lund University  Lund 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