Extended Data Fig. 8: PI3Kβ regulates STAT3 signaling via TEC Family Kinase BMX.

a, Western blot analysis of PP cells treated with AZD6482 or DMSO as a control in complete growth media or under serum/nutrient starvation conditions. Immunoblot representative of two independent experiments. b–c, Analysis of PP cells treated with AZD6482 under serum/nutrient starvation by gene expression (b; n = 3 biological replicates per condition), and Q-PCR (GM-CSF, n = 3 biological replicates per group; IL-6, n = 4 biological replicates per group) and ELISA (GM-CSF, n = 4 biological replicates per group; IL-6, n = 6 biological replicates per group) (c). For comparison of two means, unpaired, two-tail t-test with Welch’s correction assuming unequal variance. Data in (c) presented as mean values and s.d. d, PP tumor-bearing nude mice were treated with a vehicle control or AZD6482. RNA from isolated tumor cells was analyzed by RNA-Seq. Results from GSEA for AZD6482 compared to vehicle are shown (n = 3 tumors per group). e, Western blot analysis of PTEN-deficient human breast cancer cells treated with AZD6482 or DMSO as a control under reduced nutrient/serum conditions. Immunoblots representative of two biological replicates per condition. f, Immunohistochemistry analysis of HCC70 xenografts from nude mice treated with AZD6482 or a vehicle control. Representative images shown (n = 5 tumors per condition). Scale bars = 100 μm and 50 μm (inset). g–i, Western blot analysis of PP cells treated with the AKT inhibitor MK2206 (g), the TEC Kinase family inhibitor LFM-A13 (h) or the BMX inhibitor BMX-IN-1 (i) under serum/nutrient starvation conditions. Immunoblots representative of two independent experiments performed in duplicate. j, Molecular mechanisms working model. k, Summary of PDX models denoting PTEN genomic status and PTEN protein levels as assessed by IHC. Representative IHC sections are shown (n = 2 tumors per model). Scale bars, 300 μm. Apparent molecular weights in kDa are indicated for immunoblots.

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