Fig. 6.

Re-expression of wt p53 inhibits induction of polyploidy by BKM120. DG-75 and SU-DHL-10 cells were transfected with pRTS1-p53, an episomal vector system for regulated expression of wt p53. a Western blot analysis confirmed overexpression of p53 under “on” condition, which is accompanied by increased p21 expression (left). FACS analyses of cellular DNA contend in resistant SU-DHL-10 and DG-75 revealed induction of polyploidy (cells with 8n, top right panels) by BMK120 treatment, which is strongly decreased by concomitant re-expression of p53 (right panels). b Western blot analysis of SU-DHL-10 cells revealed BKM120-induced increased Cyclin B1 expression, MEK1/2 activation and decreased CDK1 Y15 phosphorylation in the absence of p53. In p53 re-expressing SU-DHL-10 cells, Cyclin B1 expression is almost completely suppressed, independently of BKM120 treatment. Furthermore activation of MEK1/2 by BKM120 is strongly reduced upon p53 expression