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. Author manuscript; available in PMC: 2013 Apr 5.
Published in final edited form as: Cancer Res. 2008 Nov 15;68(22):9323–9330. doi: 10.1158/0008-5472.CAN-08-2873

Figure 2. Bortezomib enhances UPR signaling under normoxia and hypoxia.

Figure 2

(A) ATF4 levels in HeLa cells exposed to normoxic or hypoxic conditions for 2h before treatment with DMSO or bortezomib for 6h. Thapsigargin (TH; 1μM, 4h) was used as a positivecontrol. CHOP levels in HeLa cells exposed to hypoxia 6h before treatment with DMSO or bortezomib for 12h. Thapsigargin (TH; 500nM, 12h) was used as a positive control. Nuclear protein was isolated and immunoblotted for ATF4 and CHOP; lamin A/C (loading control). (B) Active XBP-1 protein (XBP-1376aa) was induced in HeLa cells exposed to normoxia or hypoxia for 6h before treatment with DMSO or bortezomib for 18h. Thapsigargin (1μM, 12h) was used as a control. Nuclear protein was isolated and immunoblotted for XBP-1; lamin A/C (loading control). (C) HT1080-ATF4-Luc cells were treated with DMSO or bortezomib and luminescence was measured 8h later. (D) Left Panel: mice with HT1080-CMV-Luc tumors on the left flank and HT1080-ATF4-Luc tumors on the right flank were given IP injections of the vehicle or bortezomib (1mg/kg) and imaged for optical bioluminescence 8h later. Right panel: Quantitation of in vivo bioluminescence of mice shown on the left panel. Results are normalized to CMV-luc activity in untreated (vehicle-injected) animals.