Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state

作者：den Hollander Juergen; Rimpi Sara; Doherty Joanne R; Rudelius Martina; Buck Andreas; Hoellein Alexander; Kremer Marcus; Graf Nikolas; Scheerer Markus; Hall Mark A; Goga Andrei; von Bubnoff Nikolas; Duyster Justus; Peschel Christian; Cleveland John L; Nilsson Jonas A; Keller Ulrich^*

来源：Blood, 2010, 116(9): 1498-1505.

DOI：10.1182/blood-2009-11-251074

Myc oncoproteins promote continuous cell growth, in part by controlling the transcription of key cell cycle regulators. Here, we report that c-Myc regulates the expression of Aurora A and B kinases (Aurka and Aurkb), and that Aurka and Aurkb transcripts and protein levels are highly elevated in Myc-driven B-cell lymphomas in both mice and humans. The induction of Aurka by Myc is transcriptional and is directly mediated via E-boxes, whereas Aurkb is regulated indirectly. Blocking Aurka/b kinase activity with a selective Aurora kinase inhibitor triggers transient mitotic arrest, polyploidization, and apoptosis of Myc-induced lymphomas. These phenotypes are selectively bypassed by a kinase inhibitor-resistant-Aurkb mutant, demonstrating that Aurkb is the primary therapeutic target in the context of Myc. Importantly, apoptosis provoked by Aurk inhibition was p53 independent, suggesting that Aurka/Aurkb inhibitors will show efficacy in treating primary or relapsed malignancies having Myc involvement and/or loss of p53 function. (Blood. 2010;116(9):1498-1505)

• 出版日期2010-9-2