Figure 5.

Induction of Hsp70 expression upon Hsp90 inhibition is dependent on PI3K activity in MM cells. Western blot analyses of inducible Hsp70 expression upon pharmacological Hsp90 inhibition with or without concomitant PI3K inhibition in the cell lines INA-6 and MM.1S, and in primary MM cells. (A) MM.1S cells were transfected with either pSUPER or with pSUPER/PI3Kp110α, purified, and at 5 days post-transfection incubated for another 5 h with either DMSO or NVP-AUY922. INA-6 (B) or MM.1S (C) cells were incubated for 12 h with the PI3 kinase inhibitor PI103, and then subjected to treatment with 10 nM of the Hsp90 inhibitor NVP-AUY922 for another 5 h. Primary MM cells derived from a patient with plasma cell leukemia (D) or from a patient with intramedullary MM (E) were treated with DMSO or with PI103 for 12 h prior to addition of 10 nM AUY922 for another 5 h. Staining of β-actin served as a loading control.