Figure 7. c-Myc enhances E2F activity to facilitate persister development following Rb-protein reduction.
(A and B) Heatmaps of single-cell traces for CDK4/6 and CDK2 activities and Cdt1 degron intensity. MCF-7 cells expressing the c-Myc inducible construct were treated with palbociclib (1 μM) plus either DMSO (A) or doxycycline (5 μM) (B).
(C) Percentage of persisters. Data are shown as means ± SD (n = 3 biological replicates). p values were calculated using two-tailed paired t test (**p ≤ 0.001).
(D‒F) Rb and GAPDH expression (D), percentage of S-phase (E), and relative mRNA expression of E2F target genes (F) in MCF-7 cells expressing an inducible c-Myc construct. Cells were treated with palbociclib (1 μM) plus either DMSO or doxycycline (5 μM) for indicated time. Data are shown as means ± SD (n = 3 biological replicates). p values were calculated using two-tailed paired t test (*p ≤ 0.05; **p ≤ 0.001).
(G) Kaplan-Meier plots of PFS based on c-Myc genetic amplification status. The p value was calculated by the log-rank test.
(H) Representative images of pre-treatment tissue samples showing high c-Myc expression (H-score > 130) or low c-Myc expression (H-score ≤ 130). Scale bar represents 50 μm.
(I) Kaplan-Meier plots evaluating PFS in relation to c-Myc protein expression levels. p value was calculated by the log-rank test.
See also Figure S10 and S11.