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. Author manuscript; available in PMC: 2015 Nov 20.
Published in final edited form as: Cell. 2014 Nov 6;159(5):1126–1139. doi: 10.1016/j.cell.2014.10.024

Figure 5. THZ1 Inhibits MYCN-driven Transcriptional Amplification.

Figure 5

(A) Box plot depicting the log2 fold changes in actively transcribed genes in MYCN-nonamplified SH-SY5Y cells transduced with MYCN (pLenti 6.3-MYCN) compared with a control vector (pLenti 6.3). Box plot whiskers extend to 1.5 times the interquartile range (n=18,665 expressed genes; p<2.2 × 10−16, two-sided Mann-Whitney U test).

(B) Heat map of all gene expression values in MYCN-nonamplified SH-SY5Y cells vs. SH-SY5Y cells overexpressing MYCN (pLenti 6.3-MYCN) following either THZ1 (100 nM for 6 hr) or DMSO treatment. Rows show z-scores calculated for each vector.

(C) Immunoblot analysis of MYCN, CC3 and cleaved PARP in SH-SY5Y MYCN-nonamplified cells engineered to express either a control vector (pLenti 6.3) or MYCN (pLenti 6.3-MYCN) following treatment with THZ1.

(D) Heat map of differentially expressed genes in MYCN-amplified NB cells expressing a MYCN shRNA vs. control shRNA. Rows show z-scores calculated for each vector.

(E) Box plots of log2 fold changes in gene expression in MYCN-amplified NB cells expressing a MYCN shRNA vs. a control shRNA. Box plot whiskers extend to 1.5 times the interquartile range (n=18,665 expressed genes; p<10−15 for shMYCN vs. shGFP, two-sided Mann-Whitney U test).

(F) GSEA plot depicting the correlation between the top 500 downregulated genes following THZ1 treatment and the rank-ordered genes that are differentially expressed after MYCN knockdown in MYCN-amplified NB cells.

See also Figure S5.