Extended Data Fig. 8: MYC upregulation in JQ-1-resistant cells can be driven by AKT/ERK. | Nature Genetics

Extended Data Fig. 8: MYC upregulation in JQ-1-resistant cells can be driven by AKT/ERK.

From: Using antagonistic pleiotropy to design a chemotherapy-induced evolutionary trap to target drug resistance in cancer

Extended Data Fig. 8

a,b, Immunoblot analysis of MYC (a) in matched parental and JQ-1 resistant AML cells following treatment with 20μg/mL cycloheximide (CHX) for indicated times. Quantification by densitometry (b) normalized to time zero signal. c, Immunoblot analysis of phosphorylated ERK at T202/204 and phosphorylated AKT at S437 in parental and JQ-1 resistant AML cells relative to total proteins. d, Immunoblot analysis of MYC in parental and JQ-1 resistant OCI-AML2 and MV4;11 cells treated with VX11E for 24 hours. OCI-AML2 cells treated with 500nM VX11E and MV4;11 cells treated with 2μM VX11E. e,f, GI50 value of VX11E in combination with 100nM JQ-1 normalized to VX11E alone in parental and JQ-1 resistant OCI-AML2 (e) and MV4;11 (f) cells. g,h, Immunoblot analysis of MYC, NSD2 (g) and NSD3 (h) in OCI-AML2 cells following overexpression of pCDH-MYC in combination with sgRNAs targeting NSD2 (g) and NSD3 (h). i, ABT-199 8-point drug dilution series following shRNA knockdown of MYC in combination with GSK-126. e,f,i; Data are mean ± SEM for n = 3 biologically independent experiments. e,f; P-values computed by two-sided two-sample t-Test for equal means. a,c,d,g,h; Representative immunoblots of n = 3 independent experiments. Uncropped blots in Source Data.

Source data

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