Fig. 7: LEF1/TCF O’PROTAC inhibits PSG expression and growth of TMPRSS2-ERG and mutant p53-positive PCa PDX tumors. | Nature Communications

Fig. 7: LEF1/TCF O’PROTAC inhibits PSG expression and growth of TMPRSS2-ERG and mutant p53-positive PCa PDX tumors.

From: Gain-of-function mutant p53 together with ERG proto-oncogene drive prostate cancer by beta-catenin activation and pyrimidine synthesis

Fig. 7

a Sequence alignment between the DNA oligonucleotide used in LEF1/TCF O’PROTAC (OP) and the consensus DNA binding elements of each member of the LEF/TCF family. b Western blot analysis of indicated proteins in VCaP cells treated with control or LEF1/TCF OP (100 nM) for 48 h. c MTS assay in VCaP cells treated with control or LEF1/TCF OP (100 nM). d Sanger sequencing confirmation of C238Y mutation in LuCaP 23.1 PDX tumor samples. e Western blot analysis of indicated proteins in organoids derived from LuCaP 23.1 PDXs (PDXO). f–h LuCaP 23.1 PDXOs were treated with indicated OP (100 nM) and/or deoxynucleotides and harvested for Western blot analysis at 48 h after treatment (f) or cultured for 3 days followed by photographing (g) and quantification of the diameters of organoids (h). n.s., not significant. i–k Representative images of LuCaP 23.1 PDX tumors at 21 days after OP treatment (10 mg/kg every other day) (i), growth curve of tumors over the 21-day treatment period (j) and weight of tumors at day 21 of OP treatment (k). n.s., not significant. l Body weight of mice at 21 days after OP treatment as in (j). n.s., not significant. m, n Representative IHC images of the indicated proteins from tumors shown in (i) and quantification of IHC staining of the indicated proteins. See details of staining scoring and index in Methods. The western blot assays in (b, e) and (f) were repeated two independent times with similar results. Data in (c) was shown as mean ± s.d. from five replicates. Data in (h) was shown as mean ± s.d. from a total of 45 organoids randomly obtained from three independent experiments. Data in (j) and (k) were shown as mean ± s.d. from six PDXs. Data in l was shown as mean ± s.d. from six mice. Data in (n) was shown as mean ± s.d. from three independent experiments. For each experiment, five independent fields were enrolled for the calculation. Two-way ANOVA was performed in (c, j) and (l). Two-tailed Student’s t test was performed in (h, k) and (n).

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