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. Author manuscript; available in PMC: 2012 May 1.
Published in final edited form as: Nat Chem Biol. 2011 Sep 25;7(11):787–793. doi: 10.1038/nchembio.695

Figure 4. c-MYC induction confers resistance to PI3K/mTOR inhibition.

Figure 4

Figure 4

Figure 4

Figure 4

Figure 4

Figure 4

Figure 4

(a) Western blot analysis of ICN1 or control MCF10A cells treated with BEZ-235 (pg/μl) as indicated for 24 hours. Total lysates were probed with an antibody against phosphorylated ribosomal S6 kinase (Thr371) and total mTOR as a loading control (see Supplementary Fig. 20 for an uncropped version). (b) Data from the screen shows c-MYC as a significant hit for resistance to BEZ-235. (c) Relative c-MYC mRNA levels in ICN1 and c-MYC cells as determined by qRT-PCR. Shown is the fold change compared to wild-type MCF10A cells and standard deviations of 3 replicates. (d) Dose-response curve of c-MYC or control MCF10A cells treated with BEZ-235. Cells were treated for 5 days as indicated and relative cell number was measured. The data represent four independent experiments were performed in triplicate and error bars indicate standard deviations. (e) Quantitative RT-PCR of c-MYC expression in wild-type MCF10A or ICN1 cells transfected with Luciferase siRNA and ICN1 cells transfected with c-MYC siRNA pool (ICN1+si). Standard deviations of 3 replicates are indicated. (f) Dose-response curve of cells in (e) treated with BEZ-235 or vehicle for 5 days. Three replicates were performed; error bars indicate standard deviation. (g) Oncomine analysis (see Methods) of c-MYC gene copy number in PI3K/mTOR inhibitor sensitive or resistant cell lines. The red-boxed area indicates cell lines with c-MYC gene amplification (Chi square P value is indicated).

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