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. Author manuscript; available in PMC: 2021 Jun 11.
Published in final edited form as: Cancer Discov. 2020 Jul 23;10(11):1722–1741. doi: 10.1158/2159-8290.CD-20-0160

Figure 6. DUSP1 is a meningioma dependency in vitro and in vivo.

Figure 6.

(A) Cell viability of meningioma models treated with BCI. Cell viability was calculated for each model relative to DMSO control (black). p-values were calculated using one-way ANOVA. Data are represented as mean +/− SD. (B) Downregulation of DUSP1 following treatment with the BET bromodomain inhibitor (+)-JQ-1. Cells were treated for 24 hours with a range of concentrations and then assayed for DUSP1 expression by qPCR. Data are represented as mean +/− SD. (C) Time course of cell viability following knockdown of DUSP1 in IOMM-Lee cells vs. non-targeting control. Conditions were compared using student’s t-test. Data are represented as mean +/− SD. (D) Depletion of DUSP1 following transduction of one of two DUSP1-targeting shRNAs versus non-targeting control in IOMM-Lee cells. Data are represented as mean +/− SD. (E) Time course of cell viability following knockdown of DUSP1 in DI-134 cells vs. non-targeting control. Conditions were compared using student’s t-test. Data are represented as mean +/− SD. (F) Depletion of DUSP1 following transduction of one of two DUSP1-targeting shRNAs versus non-targeting control in DI-134 cells. Data are represented as mean +/− SD. (G) Western blot to assay targets of DUSP1 and markers of apoptosis following treatment with 5 μM of DUSP1/6 inhibitor. (H) Survival following intracranial xenograft of the meningioma model CH157-MN immunodeficient mice. Meningioma cells were transduced with non-targeting control shRNA (black line) or one of two independent shRNAs targeting DUSP1 (red lines). p-values were calculated using a logrank test. (I) DUSP1 expression in CH157-MN cells after transduction with non-targeting control or one of two independent shRNAs targeting DUSP1, prior to intracranial implantation into mice. p-values were calculated using Student’s t test. (J) Tumor weight following treatment with DUSP1/6 inhibitor in mice subcutaneously implanted with CH157-MN cells was compared following two weeks of treatment with DMSO (black) or BCI (red). Tumor weights were compared using Wilcoxon rank-sum test. Boxplots are represented as the median plus interquartile range. (K) Tumor volume following treatment with DUSP1/6 inhibitor in mice subcutaneously implanted with CH157-MN cells was compared following two weeks of treatment with DMSO (black) or BCI (red). Tumor volumes were compared using Wilcoxon rank-sum test. Boxplots are represented as the median plus interquartile range. (L) Image of tumors from mice treated with DMSO (top) or BCI (bottom). P-values were calculated by Student’s t test for <3 comparisons, or by ANOVA followed by Tukey’s honest significant different for ≥3 comparisons. *p< 0.05,**p<0.005, ***p<0.0.0005