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. Author manuscript; available in PMC: 2017 Mar 14.
Published in final edited form as: Cancer Cell. 2016 Mar 14;29(3):255–269. doi: 10.1016/j.ccell.2016.02.006

Figure 4. The cyclin D1-CDK4 axis mediates resistance to HER2-targeted therapy.

Figure 4

(A) Fold change in CCND1 gene expression in cell lines after treatment with lapatinib 500nM for 6 hours. (B) Western blots on cell lysates after treatment with lapatinib 500nM or DMSO for 24 hours (NB: for cleaved PARP blots, upper band represents total PARP and lower band cleaved PARP). (C) Sensitivity to lapatinib or trastuzumab (IC50) of SKBR3/BT474 cells constitutively overexpressing CCND1 or empty vector (EV). (**p≤0.01, ***p≤0.001 by one-way ANOVA). (D) Relative viability of MDA-MB-453 tet-shCCND1 and MDA-MB-361 tet-shCCND1 cells in response to trastuzumab in the presence or absence of doxycycline. (E) Design of clinical trial NCT00148668 (TCH – docetaxel, carboplatin, trastuzumab; VH – vinorelbine, trastuzumab) (F) CCND1 copy number (determined by a Global Parameter Hidden Markov Model) by pathological complete response (CR) status in the NCT00148668 trial. Each dot represents an individual patient and lines represent means (*p=0.016 by Wilcoxon signed rank test). All error bars represent SD. See also Figure S4.