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

Figure 3

Chemotherapy-Induced SASP in Culture and In Vivo

(A) Overall correlation between XRA and mitoxantrone (MIT)-induced SASPs for all three prostate epithelial cancer cell lines (BPH-1, RWPE-1, and PC-3). Correlations for the individual cell lines are given in the table to the right. The senescence inducer (XRA or MIT) is given in parentheses.

(B–E) Human tumor cells were isolated from biopsies obtained from the same patient before MIT chemotherapy and from prostate tissue following prostatectomy after MIT chemotherapy. Laser captured cells were analyzed by quantitative RT-PCR for the mRNAs encoding the indicated proteins, as described in Materials and Methods and Text S1. The results are displayed on a log10 scale indicating the values before (horizontal or x-axis) compared to after (vertical or y-axis) chemotherapy (top left panel in [B]). Each black dot in (B, C, and D) represents the results obtained from a single patient. The average values for all patients before versus after chemotherapy are indicated by a red dot (B–D); these values are also represented as a heat map in (E).

(B) Values for mRNAs encoding proteins associated with senescence (p16 and p21) and proliferation (cyclin A, MCM-3, and PCNA).

(C) Values for mRNAs encoding SASP-associated proteins (IL-6, IL-8, GM-CSF, GRO-α, IGFBP-2, and IL-1β).

(D) Value for an mRNA encoding a non-SASP–associated protein (IL-2).

(E) Averages for the values shown in (B–D). Overall p-values, determined by the Student t-test, and number of paired samples (or patients) analyzed for each mRNA are given to the right of the heat map. Signals higher than the prechemotherapy baseline are shown in red; signals below baseline are displayed in green.

Figure 3

doi: https://doi.org/10.1371/journal.pbio.0060301.g003