Research Paper Volume 13, Issue 12 pp 16178—16197

GPR30-mediated HMGB1 upregulation in CAFs induces autophagy and tamoxifen resistance in ERα-positive breast cancer cells

HMGB1-induced autophagy is required for mammary tumor resistance to tamoxifen in mice. MCF-7 cells mixed with CAFs or engineered CAFs (CAF/sh-NC, CAF/sh-GPR30) were subcutaneously transplanted into nude mice. Mice were treated with tamoxifen as described in the Materials and Methods. (A) Tumor size in mice; mean ± SE of triplicate representative experiments. (B) Tumor volume was assessed. (C) Autophagy- and apoptosis-related markers in xenografts were quantified by western blotting. U0126 injected into mice at 25 mmol/kg. (D, E) The concentration of HMGB1 in xenograft tissues and blood from mice. (F) Representative images of LC3B, GPR30, and HMGB1 examined by IHC staining are shown; Scale bar, 50 μm.

Figure 6. HMGB1-induced autophagy is required for mammary tumor resistance to tamoxifen in mice. MCF-7 cells mixed with CAFs or engineered CAFs (CAF/sh-NC, CAF/sh-GPR30) were subcutaneously transplanted into nude mice. Mice were treated with tamoxifen as described in the Materials and Methods. (A) Tumor size in mice; mean ± SE of triplicate representative experiments. (B) Tumor volume was assessed. (C) Autophagy- and apoptosis-related markers in xenografts were quantified by western blotting. U0126 injected into mice at 25 mmol/kg. (D, E) The concentration of HMGB1 in xenograft tissues and blood from mice. (F) Representative images of LC3B, GPR30, and HMGB1 examined by IHC staining are shown; Scale bar, 50 μm.