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. Author manuscript; available in PMC: 2017 Sep 1.
Published in final edited form as: Mol Cancer Ther. 2017 Jan 30;16(3):516–528. doi: 10.1158/1535-7163.MCT-16-0552

Figure 5. HGF-mediated resistance to trametinib is dependent on PI3Kβ-sparing isoforms in UM cells.

Figure 5

(A) Isoform specific PI3K inhibitors differentially block HGF-mediated activation of AKT in UM cells. UM004 cells were pretreated with increasing doses of GDC0032, TGX221, BYL719 and IPI145 for 6 hours. Cells were then stimulated with 10 ng/ml HGF for 30 minutes. Cell lysates were probed with pAKT, AKT, PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ and actin antibodies. (B) PI3Kβ-sparing inhibitor GDC0032, but not PI3Kβ inhibitor TGX221, abrogates HGF-mediated resistance to trametinib in UM cells. UM004 cells were treated 50 nM trametinib, 10 ng/ml HGF, 0.5 µM of GDC0032, TGX221, BYL719 or IPI145 respectively or in combination for 48 hours. Cells were stained with crystal violet. Representative microscopic images are shown (100× magnification). Scale bar is equal to 100 µm. The percentage of crystal violet is normalized to vehicle control and the mean of percentage crystal violet from triplicate experiments is shown. *P<0.05, **P<0.01, ***P<0.001, ns: not significant.