Figure 5.

Leukemia inhibitory factor receptor (LIFR) overexpression leads to signal transducer and activator of transcription 3 (STAT3) activation and limits the anticancer effect of trastuzumab‐emtansine (T‐DM1). A, Phosphorylation of growth factor receptors and expression of cytokine receptors in BT‐474 and BT‐474/KR cells on western blotting. B, mRNA of LIFR and LIF in BT‐474 and BT‐474/KR cells on quantitative reverse transcription‐polymerase chain reaction. C, BT‐474/KR cells were transfected with either non‐targeting control (NTC) small interfering RNA (siRNA) or LIFR siRNA for 48 h. LIFR knockdown efficiency and STAT3 activation were measured on western blotting. D, BT‐474/KR cells were transfected with the indicated siRNA for 48 h, followed by treatment with T‐DM1 (0.1 μg/mL) for an additional 96 h. Cell survival was analyzed on sulforhodamine B assay. Error bars represent mean ± SD from triplicates. **P < .01, ***P < .001. GM‐CSFR, granulocyte‐macrophage colony‐stimulating factor receptor; IL‐6R, interleukin‐6 receptor; pEGFR, phospho‐EGFR; pFGFR1, phospho‐FGFR1; pHER3, phospho‐HER3