Extended Data Fig. 2: CHD1^Del confers resistance to castration in SPOP^Mut PCa.

a-b, Histologic analysis of Ki67 and Cleaved caspase-3 in PCSp prostate tumors with or without surgical castration (n = 3 tumors per group). Tumors that showed response or resistance to castration were compared. Representative images are from anterior prostate (AP) lobes. Cx: Castration. Scale bar = 50 μm. c, Western blot assays of MyC-Cap cells expressing SPOP^Mut (W131G) with or without Chd1 knockout (KO). Sp, SPOP^W131G; CSp, SPOP^W131G/Chd1^KO. d, Growth curves of Sp and CSp MyC-CaP cells overexpressing vector control (CSp-Vec) or CHD1 (CSp-CHD1) cultured in medium supplied with regular FBS (Normal) or charcoal-stripped FBS (CS). n = 3 biological replicates. e, MYC IHC staining in Sp and CSp MyC-Cap tumors with or without castration. Scale bar = 50 μm. f, Quantification of Ki67 IHC staining in Sp and CSp MyC-Cap tumors with or without castration (n = 3 tumors per group). g, Western blot assays of LNCaP cells expressing SPOP mutation (W131G) with or without Chd1 knockout (KO). Sp, SPOP^W131G; CSp, SPOP^W131G/CHD1^KO. h, Quantification of Ki67 IHC staining in Sp and CSp LNCaP xenograft tumors with or without castration (n = 3 tumors per group). i, Western blot assays of LAPC4 cells expressing SPOP mutants with or without CHD1 depletion. j, Growth curves of SPOP^Mut LAPC4 cells with or without CHD1 depletion cultured in medium supplied with regular FBS (Normal) or charcoal-stripped FBS (CS) (n = 3 biological replicates per group). Data in b, d, f, h and j are presented as the mean ± standard deviation. Experiments were performed at least three times with similar results. Two-tailed unpaired Student’s t-test (d and j) or one-way ANOVA with Tukey’s post hoc tests (b, f, and h) was performed using GraphPad Prism v.9.2.0.

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