Fig. 7: Stromal AR in Gli1-lineage cells induces basal epithelial IGF and Wnt pathways to promote oncogenic growth through paracrine action.

a IGF1 concentration in conditioned media (CM) from 12-week-old Hi-Myc:R26^mTmG/+:Gli1^CreER/+ and Hi-Myc:R26^mTmG/+:Ar^L/Y:Gli1^CreER/+ GFP⁺ cells. Data are represented as mean ± SD of four independent samples over two biological replicates. Two-sided t test, ^**p < 0.01. Source data and the exact p values are provided as a Source Data file. b Organoid culture of prostatic epithelial cells from 12-week-old Hi-Myc:R26^mTmG/+:Gli1^CreER/+ and Hi-Myc:R26^mTmG/+:Ar^L/Y:Gli1^CreER/+ mice, following treatment with Hi-Myc:R26^mTmG/+:Gli1^CreER/+ CM, Hi-Myc:R26^mTmG/+:Gli1^CreER/+ CM + IGFBP3 (1 μg/ml), or Hi-Myc:R26^mTmG/+:Ar^L/Y:Gli1^CreER/+ CM. Representative brightfield images and HE staining showing organoid morphology and structure observed in indicated groups. Scale bars, 400 μm and 25 μm. c Representative images of triple-IF staining for indicated antibodies on prostate tissues from Hi-Myc:R26^mTmG/+:Gli1^CreER/+ and Hi-Myc:R26^mTmG/+:Ar^L/Y:Gli1^CreER/+ mice. Yellow or white arrows indicate CK14⁺Myc⁺ or CK14⁺pIGF1R⁺ basal epithelial cells respectively. Blue arrows indicate IGFBP3⁺ mGFP⁺ stromal cells. Scale bars, 20 μm. d Schematic of hypothetic models by which stromal AR in Gli1-lineage cancer-associated fibroblast (CAF) cells regulate prostate tumorigenesis via IGF, Wnt, and other signaling pathways in prostatic basal epithelial cells. e GSEA results from pre-ranked differentially expressed genes list comparing basal cells versus luminal cells in human prostate cancer samples, Hi-Myc:R26^mTmG/+:Gli1^CreER/+ and Hi-Myc:R26^mTmG/+:Ar^L/Y:Gli1^CreER/+ mice. See also “Methods” section.