Fig. 1: Smad4 and Apc co-deletion leads to penile squamous cell carcinoma in mice.

a, b IHC stain for AR in human penile tumors (n = 8) and normal mouse penis (n = 5). Scale bar 100 μm. c, d Morphology and fluorescence for resected mouse penises of indicated genotype and age. Scale bar 2 mm. e Penile prolapse free survival curves for mice of three genotypes with n indicated. ****P < 0.0001, log-rank test. f Morphology and fluorescence for resected mouse penis of SAm genotype at 6.4 months of age, with GFP⁺ tumor nodules clearly visible. Scale bar 2 mm. g, h H&E stain of penis and prostate lobes (anterior AP, dorsolateral DLP) of SA mouse at 6.8 month of age. White arrows denote keratin pearls. Scale bar 100 μm. i SA males at 8–12 weeks underwent castration or mock surgical procedure. After 4 weeks, the mice were euthanized. The serum testosterone was measured with ELISA for the mice and age-matched wild type (WT) males were used as control (n = 6 for each group). j Representative images of the mouse penis at each week post-surgery. k, l Weight, representative image and H&E staining of resected penises from WT control or SA mice 4 weeks post-surgery. Scale bar 10 mm and 200 μm (n = 8 for WT, n = 6 for mock and castration). In i, k, data represent mean ± SD. ^#P > 0.05, ***P < 0.001, ****P < 0.0001, two-sided Student’s t test.