Figure 2: mTOR-dependent re-expression of ERRα in lapatinib-resistant cells.
From: ERRα mediates metabolic adaptations driving lapatinib resistance in breast cancer
(a) Dose-dependent curves of normalized cell index for pSKBr3 and for lapatinib-resistant SKBr3 (LRSKBr3) cells on C29 treatment and exposed to varying concentration of lapatinib. Error bars are s.d.’s from three independent replicates, statistical significance is calculated in C29-treated cells relative to vehicle using unpaired Student’s t-test (**P<0.01; ***P<0.001). (b) Expression of ERRα or veh treatment (left panel). Expression of ERRα in parental (pSKBr3) and in LRSKBr3 cells, in parental and in lapatinib-resistant BT-474 and in parental (NIC-5231) and in resistant cells on 24-h lapatinib or veh treatment. (c) Expression of mTOR, S6, P-S6, 4E-BP and P-4E-BP in pSKBr3 and LRSKBr3 cells on 24-h lapatinib or veh treatment. (d) Expression of ERRα, S6 and P-S6 in pSKBr3 (left) and LRSKBr3 (right) cells on 24-h lapatinib or veh treatment in presence or absence of rapamycin treatment. (e) Expression of ERRα in ERBB2-dependant mouse mammary NIC tumours following acute treatment with lapatinib for 48 h (left panel). (f) Expression of ERRα in HER2-positive PDX tumour following treatment with lapatinib for 48 h. (g) Growth curves representing the tumour volume of ERBB2-dependant mammary NIC tumors upon long-term lapatinib (n=6) or veh (n=5) treatment. Error bars are SEM. (h) Immunohistochemical (IHC) staining of ERRα expression in NIC tumours. Bottom right panel—quantification of IHC staining. Scale bar, 50 μM. Error bars are s.e.m., P values generated using unpaired Student’s t-tests. (i) Expression and activity of ErbB2 and downstream effectors in ErbB2-dependant NIC mouse mammary tumours following acute treatment with lapatinib for 48 h and on lapatinib relapse.
