{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T09:49:34Z","timestamp":1760953774829},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2010,11,19]],"date-time":"2010-11-19T00:00:00Z","timestamp":1290124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold> Aurora kinases represent promising novel cancer therapy targets. Genomic analyses of human cutaneous melanoma (CMM) models (<jats:italic>N<\/jats:italic>\u2003=\u200351, low passage) by classical and\/or array CGH revealed frequent gains at chromosome 20q (65%, amplifications in 45%) repeatedly including the Aurora A gene locus. Accordingly, the majority of CMM cell cultures overexpressed Aurora A when compared to proliferating non\u2010malignant cells. Moreover, CMM cells even when arrested in G1\/S cell cycle phase contained readily detectable levels of Aurora A indicating incomplete degradation during mitosis. Already at low concentrations (10\u2013100\u2003n<jats:sc>m<\/jats:sc>), long\u2010term (7\u201310\u2003days) application of the pan\u2010Aurora kinase inhibitor VE\u2010465 completely prevented colony formation in all CMM models tested. In contrast, blockade of cell survival\/proliferation and DNA synthesis as well as the induction of apoptosis by VE\u2010465 distinctly differed in short\u2010term experiments (up to 72\u2003h exposure). Both cell cycle arrest and DNA synthesis blockade depended on the level of VE\u2010465\u2010mediated p53\/p21 activation while p53\/p21 unresponsiveness led to repetitive endoreduplication (&gt;8n DNA content). In contrast, apoptosis induction by VE\u2010465 and Aurora A siRNA did not correlate with p53\/p21 responsiveness and DNA synthesis blockade. Moreover, application of the Aurora B\u2010specific inhibitor ZM447439 and siRNA was less efficient to induce CMM cell death proofing that apoptosis induction by VE\u2010465 depended predominantly on Aurora A targeting. In combination experiments with chemotherapeutic agents, VE\u2010465 acted additive to antagonistic when applied concomitantly but in several cases even synergistic when applied consecutively. In summary, we suggest that the Aurora A kinase might represent a promising target of well\u2010designed novel antimelanoma strategies.<\/jats:p>","DOI":"10.1111\/j.1600-0625.2010.01182.x","type":"journal-article","created":{"date-parts":[[2010,11,19]],"date-time":"2010-11-19T06:31:19Z","timestamp":1290148279000},"page":"1040-1047","source":"Crossref","is-referenced-by-count":15,"title":["Response of experimental malignant melanoma models to the pan\u2010Aurora kinase inhibitor 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