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Figure 1 | Breast Cancer Research

Figure 1

From: Lapatinib–induced NF-kappaB activation sensitizes triple-negative breast cancer cells to proteasome inhibitors

Figure 1

Lapatinib induces NF-κB activation in an off-target manner. (A-F) Lapatinib induces p65 phosphorylation in both HER2-positive and triple-negative breast cancer cells. HER2-postive SkBr3 and BT474 breast cancer cells were treated with or without 1 μM lapatinib for two days, and SkBr3/Lap and BT474/Lap cells were cultured in the presence of 1 μM lapatinib (A). Triple-negative MDA-MB-231 and MDA-MB-468 breast cancer cells were treated with 1 μM lapatinib for the indicated days (B). SkBr3/Lap#6 cells were treated with 10 μM IKK inhibitor II, 20 μM IKK inhibitor X, or 5 μM IKK inhibitor VII for two days (C). Lapatinib-selected clones established from triple-negative MDA-MB-231, MDA-MB-468, and HBL-100 cell lines were cultured in the presence of 1 μM lapatinib (D). Erlotinib- and gefitinib-selected clones established from BT474 (E) and MDA-MB-231 cells (F) were cultured in the presence of 1 μM respective drugs. Total lysates prepared from these cells were subjected to Western blot analysis with the indicated antibodies for NF-κB phosphorylation and expression. (G, H) Lapatinib treatment induces p65 nuclear translocation. MDA-MB-231 and 231/Lap#2 cells were subjected to nuclear/cytoplasmic fractionation followed by Western blot analysis with the indicated antibodies. Lamin and tubulin function as control markers for nuclear and cytosolic extraction, respectively (G). MDA-MB-231 and 231/Lap#6 cells were fixed followed by staining with anti-p65 antibody and DAPI (fluorescent dye for nucleus staining) in confocal microscope analysis (H). DAPI, diamidino-2-phenylindole; IKK, IKB kinase; HER2, human epidermal growth factor receptor 2.

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