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. Author manuscript; available in PMC: 2021 Jul 13.
Published in final edited form as: Cancer Res. 2021 Jan 28;81(4):847–859. doi: 10.1158/0008-5472.CAN-20-1822

Figure 5. CREBBP loss sensitises cells to CDK4/6i.

Figure 5

(A) Dose response curves of HAP1 WT and CREBBPmut cells treated with increasing concentrations of the clinical CDK inhibitors Ribociclib, Abemaciclib, Palbociclib and SNS-023 at the concentrations indicated. (B) Western blot of protein lysates of HAP1 WT and CREBBPmut cells treated with 1μM of Palbociclib or DMSO for 48hrs showing suppression of specific phospho sites in CREBBPmut cells. (C) Bar chart of relative mRNA expression of FOXM1 target genes in HAP1 WT and CREBBPmut cells +/- Palbociclib (250nM), Abemaciclib (500nM) or DMSO treatment at 24 hours after cell seeding for 72hrs. Gene expression was quantified using RT-PCR. (D) Dose response curves of a panel of non-isogenic cancer cell lines (WT= lung: A549, H1299, colorectal: HCT116, and CREBBPmut lung NCI-H520, endometrial AN3CA, leukaemia NALM-6, and lymphoma SU-DHL-6 and NU-DHL-1) spheroids treated with increasing concentrations of Palbociclib for five days and displayed according to CREBBP status. (E) Bar chart of SF50 values of non-isogenic CREBBPmut and WT cell lines grown as spheroids and treated with Palbociclib for 5 days.