Fig. 5: ATF6 sustains mTOR activation and HSP90 expression during ER stress which stabilizes BRCA-1 and prevents its proteasomal degradation.
From: ATF6 prevents DNA damage and cell death in colon cancer cells undergoing ER stress
RKO and HCT116 cells were pre-treated or not with ceapinA7 (12 μM) for 1 h and then treated or not with DPE (100 μM) or Thapsigargin (Tg) (30 nM) or left untreated, as control. A, B Protein expression level of HSP90, p-mTOR, mTOR, p-4EBP1, and 4EBP1 was evaluated by western blot analysis. β-Actin was used as loading control. The histograms represent the densitometric analysis of the ratio of specific protein and the appropriate control of three different experiments. Data are represented as the mean plus S.D. *p-value < 0.05. C RKO cells were pre-treated or not with NVP-BEZ-235 (250 nM) for 1 h and then treated or not with DPE (100 μM) or left untreated, as control. Protein expression level of BRCA-1, HSP90, p-4EBP1, and 4EBP1 was evaluated by western blot analysis. β-Actin was used as loading control. The histograms represent the densitometric analysis of the ratio of specific protein and the appropriate control of three different experiments. Data are represented as the mean plus S.D. *p-value < 0.05. D RKO cells were pre-treated or not with ceapinA7 (12 μM) for 1 h and then treated or not with DPE (100 μM) for 48 h. To evaluate proteasomal degradation cells were incubated or not with Bortezomib (bz) (10 nM) for the last 4 h of treatments. Western blot analysis of BRCA-1 expression level. β-Actin was used as loading control and one representative experiment is shown. The histograms represent the densitometric analysis of the ratio of BRCA-1/β-Actin of three different experiments. Data are represented as the mean plus S.D. p value: *< 0.05.
