You have accessJournal of UrologyProstate Cancer: Basic Research IV1 Apr 2010544 PROSTATE SPECIFIC DELETION OF THE MISMATCH REPAIR (MMR) GENE MLH1 IN MICE CAUSE NEOPLASTIC ALTERATIONS OF THE PROSTATE Burkhard Kneitz, Cora Reiß, Patrick Adam, Philip Ströbel, Hubertus Riedmiller, and Martin Spahn Burkhard KneitzBurkhard Kneitz Würzburg, Germany More articles by this author , Cora ReißCora Reiß Würzburg, Germany More articles by this author , Patrick AdamPatrick Adam Tübingen, Germany More articles by this author , Philip StröbelPhilip Ströbel Mannheim, Germany More articles by this author , Hubertus RiedmillerHubertus Riedmiller Würzburg, Germany More articles by this author , and Martin SpahnMartin Spahn Würzburg, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.764AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Defects in the mismatch repair system have been identified in prostate cancer. In addition a prognostic role for altered expression in mismatch repair genes has been suggested in colorectal cancer as well as in prostate cancer. To understand the molecular basis of prostate cancer (PCa) development, progression and metastasis caused by MMR defects we generated a mouse model to disrupt Mlh1 by Cre/loxP mediated recombination exclusively in prostate tissue. METHODS Pathways mediated by Pten are frequently altered in prostate carcinoma. To test in addition synergistic effects of Pten deficiency and defects of the MMR system in prostate cancer development we inactivated both, Pten and Mlh1, in the prostate epithelium of the mouse. RESULTS We showed an efficient and specific deletion of MLH1 in prostate epithelium of the Mlh1p-/- mouse. Inactivation of Mlh1 in the Mlh1p-/- mouse leads to prostatic intraepithelial neoplasia after 52 weeks of age. Thus our study demonstrate that loss of MMR activity in the epithilial cells of mouse prostate causes early stages of prostate cancer at late latencies. It was already shown that loss of Pten in mouse prostate epithelium leads to neoplastic transformation in prostatic tissue. Inactivation of both Pten and Mlh1 in mice resulted in rapidly developing prostatic intraepithelial neoplasia. We found initiation stages of prostate cancer with intraephithelial neoplasia, followed by progression to invasive adenocarcinomas with defined kinetics.Using this mouse lines we generated unique models to study PCa development caused by MMR defects. CONCLUSIONS Our results demonstrate that loss of Mlh1 mediated MMR activity caused initiation of hyperproliferative prostatic disease followed by neoplastic alterations of the prostate with late latencies. In addition we found a synergy of Mlh1 and Pten deficiency for the development of prostate cancer. This new mouse models should be valuable for providing new genetic and molecular insight into the pathogenesis of MMR defective prostate cancer. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e214 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Burkhard Kneitz Würzburg, Germany More articles by this author Cora Reiß Würzburg, Germany More articles by this author Patrick Adam Tübingen, Germany More articles by this author Philip Ströbel Mannheim, Germany More articles by this author Hubertus Riedmiller Würzburg, Germany More articles by this author Martin Spahn Würzburg, Germany More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...