BRCA1-IRIS overexpression promotes intrinsic and acquired paclitaxel resistance in TNBC cells. (A) The survival of HME, HME/IRIS and the indicated TNBC cell lines following treatment with increasing concentrations of paclitaxel. Values are means of triplicates done three separate times. Inset shows BRCA1-IRIS expression in these cell lines following exposure to increasing concentrations of paclitaxel. (B) The expression of the indicated proteins following treatment with vehicle or paclitaxel (5 μM) for 24 h or MDA-MB-468 previously silenced from luciferase or BRCA1-IRIS for 48 h. (C) The expression of the indicated proteins in HME or HME/IRIS cells following exposure to 0, 10, 20 or 30 μM of paclitaxel. (D) The expression of the indicated proteins in HME or HME/IRIS cells following exposure to 1 μM of paclitaxel for 0, 1 or 3 weeks. (E and F) The expression of the indicated proteins in the nucleus or cytoplasm of HME or HME/IRIS following exposure to 1 μM of paclitaxel for 0, 1 or 3 weeks. Activated ERK, JNK and p38 were detected using antibodies specifically detect p-T202/Y204-ERK, p-T183/Y185-JNK, and p-T180/Y182-p38. (G) The effect of BRCA1-IRIS overexpression on the proliferation of HME cells. (H) The effect of inhibiting ERK (using PD98059), JNK (using SP600125), p38 (using SB203580), PI3′K/AKT (using LY294002), EGFR (using Erlotinib), ErbB2 (using CP-724714), EGFR/ErbB2 (using Lapatinib), and EGFR/ErbB2/ErbB3 (using Sapitinib) on the survival of HME or HME/IRIS cells. Values represent the means of experiments that were performed in triplicate done three separate times, *** = P ≤0.001 (compared to control in each cell line).
(I) Schematic representation of the data so far. EGFR, ErbB2 and ErbB3, epidermal growth factor receptor 1, 2 and 3, respectively; HME, human mammary epithelial cells; TNBC, triple negative breast cancer.