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Among these, autonomous parvoviruses (PV), like MVMp (minute virus of mice) and H\u20101PV are being explored as candidates for cancer gene therapy. Human PDAC cell lines were identified to display various susceptibilities to an infection with H\u20101PV. The correlation between the integrity of the transcription factor SMAD4, mutated in 50% of all PDAC, and H\u20101PV permissiveness was particularly striking. Indeed, mutation or deletion of SMAD4 dramatically reduced the activity of the P4 promoter and, consequently, the accumulation of the pivotal NS1 protein. By means of DNA affinity immunoblotting, novel binding sites for SMAD4 and c\u2010JUN transcription factors could be identified in the P4 promoter of H\u20101PV. The overexpression of wild\u2010type SMAD4 in deficient cell lines (AsPC\u20101, Capan\u20101) stimulated the activity of the P4 promoter, whereas interference of endogenous SMAD4 function with a dominant\u2010negative mutant decreased the viral promoter activity in wild\u2010type SMAD4\u2010expressing cells (Panc\u20101, MiaPaCa\u20102) reducing progeny virus production. In conclusion, the importance of members of the SMAD family for H\u20101PV early promoter P4 activity should guide us to select SMAD4\u2010positive PDACs, which may be possible targets for an H\u20101PV\u2010based cancer therapy.<\/jats:p>","DOI":"10.1002\/ijc.24992","type":"journal-article","created":{"date-parts":[[2009,10,23]],"date-time":"2009-10-23T17:05:34Z","timestamp":1256317534000},"page":"2914-2927","source":"Crossref","is-referenced-by-count":25,"title":["SMAD4: a predictive marker of PDAC cell permissiveness for oncolytic infection with parvovirus H\u20101PV"],"prefix":"10.1002","volume":"126","author":[{"given":"Sebastian","family":"Dempe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra 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