Figure 3. MK2-deficient tumors dominate the total tumor progression over time in a manner that is dependent on the loss of p53.

(A, B) Quantification of MK2^CV/CV;Kras^G12D/+;p53^Δ/Δ tumors at weeks 6, 9 and 12 after tumor induction and at experimental endpoint (final): MK2+ and MK2− tumor areas are shown as percentage of total lung area (A) and relative percentages of total tumor burden (B). (A–D): n = 4–5 mice per time point, *: p ≤ 0.02, error bars indicate SEM.

(C–D) Quantification of MK2^CV/CV;K-ras^G12D/+;p53^+/+ tumors at weeks 9 and 12 after tumor induction and at experimental endpoint (final): MK2+ and MK2− tumor areas shown as percentage of total lung area (C) and relative percentages of total tumor burden (D).

(E) Generation of isogenic MK2+ and MK2− Kras^G12D/+;p53^Δ/Δ murine NSCLC cell lines.

(F) PCR analysis of two isogenic MK2+ and MK2− murine NSCLC cell line pairs, A and B, before (−Cre) and after infection with Adeno-Cre (+Cre). Initial cell lines harbored one MK2 expressing (+CV) and one MK2 negative (–CV) allele. After Cre infection, selected clones inverted one allele, resulting in homocygous MK2^+CV/+CV (MK2+) or MK2^−CV/−CV (MK2−) cells.

(G) Western Blot of isogenic MK2+ and MK2− murine NSCLC cell line pairs. β-actin: loading control.

(H) Ratio of doubling times between MK2+ and MK2− isogenic cell lines A and B. (G–H): n = 3 independent experiments, *: p<0.02, **: p<0.008, *** p<0.001, error bars = SEM.

(I) Ratio of doubling times between H1299 cells stably expressing a control hairpin (MK2+) or hairpin against MK2 (MK2−) and A549 cells with or without siRNA against MK2 in combination with or without siRNA against 53.