AZD5363 regulates MYC signaling in PTEN-deficient DLBCLs. (A) Treatment with 1 µM AZD5363 for 6 and 24 hours results in increased phosphorylation of AKT and decreased PRAS40 phosphorylation in BJAB, K422, and U2932 cells measured by western blotting. (B) Treatment with 1 µM AZD5363 for 6 and 12 hours results in increased phosphorylation of AKT and decreased PRAS40 phosphorylation in UP4FD cells measured by western blotting. (C) GEP following AZD5363 treatment in K422 and U2932 cells. Changes of gene expression are profiled at the indicated time points following treatment with AZD5363. Gene expression changes are depicted according to the color scale shown. Genes that are involved in critical biological processes are highlighted. (D) Gene set enrichment analysis of a previously described MYC gene expression signature. The MYC signature is significantly enriched with genes that are downregulated following AZD5363 treatment in K422 and U2932 cells. (E) AKT inhibition following treatment with 1 µM AZD5363 for 6 and 24 hours results in decreased MYC expression measured by western blotting in BJAB, K422, and U2932 cells. (F) Expression of an MYC cDNA partially rescues BJAB and U2932 cells treated with AZD5363. In contrast, expression of an MYC cDNA does not rescue cells from doxorubicin-induced toxicity. Expression of exogenous MYC protein is shown by western blotting. Representative results from at least 3 independent replicates are shown. Error bars indicate standard deviations.