Advertisement

< Back to Article

Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor

Figure 5

Oncogenic RAS Amplifies the SASP

(A) Soluble factors produced by the indicated fibroblasts were analyzed by antibody arrays and displayed as described for Figure 1A, but in this case, PRE signals were used as the baseline. Therefore, color intensities represent log2-fold changes of SEN CM relative to PRE CM from cells of the same genotype under the same culture conditions. We pooled and averaged highly correlated data (see Figure 1C) from cells originating from a common tissue (WI-38, IMR-90 from embryonic lung; and HCA-2, BJ from neonatal foreskin), and from senescence induced by REP or XRA. Details of the data processing are provided in Datasets S9S12. The senescence inducer is given in parentheses. Signals higher than baseline are shown in yellow; signals below baseline are displayed in blue. The numbers on the heat map key (right) indicates log2-fold changes from the baseline.

(B) WI-38 cells induced to senesce by RAS were immunostained for the SASP proteins IL-6 and IL-8, and the senescence marker p16INK4a.

(C) Correlations between SASPs induced by RAS versus REP or XRA in fibroblasts from embryonic lung (WI-38, IMR-90, left) or neonatal foreskin (HCA-2, right). Correlations for the individual cell strains and senescence inducers are given in the tables below the graphs.

(D) Shown are the log2-fold values for factors that are significantly increased in CM from fibroblasts induced to senesce by RAS compared to fibroblasts induced to senesce by XRA or REP. Green indicates SEN WI-38 and IMR-90 cells induced to senesce by RAS versus XRA. Red indicates SEN WI-38 and IMR-90 induced to senesce by RAS versus REP. Gray indicates HCA2 cells induced to senesce by RAS versus XRA. Blue indicates HCA2 cells induced to senesce by RAS versus REP.

(E) Shown are the log2-fold values for factors that are uniquely and significantly increased in CM from fibroblasts induced to senesce by RAS compared to PRE CM, but not significantly changed in CM from fibroblasts induced to senesce by XRA or REP. The color code is identical to (D).

(F) Soluble factors from CM produced by the indicated epithelial cells were analyzed by antibody arrays and displayed as described for Figure 1A, using PRE CM as the baseline. Signals higher than baseline are shown in yellow; signals below baseline are in blue. Asterisks (*) indicate factors conserved between fibroblasts and epithelial cells.

(G) Correlations between SASPs induced by RAS versus XRA in prostate epithelial cells.

Figure 5

doi: https://doi.org/10.1371/journal.pbio.0060301.g005