Figure 6. Androgen signaling plays a promotional role in oncogenic transformation induced by stabilized β-catenin in p63-expressing cells.

A. Illustration of transgenic alleles present in R26hAR^L/+Ctnnb1^fl(Ex3)/+p63^CreERT2/+ mice. Expression of the R26hAR^L/+transgene is driven by a modified CAG promoter and is activated by Cre-mediated removal of a Lox-Stop-Lox neomycin cassette. B. Schematic of experimental timeline. R26hAR^L/+Ctnnb1^fl(Ex3)/+p63^CreERT2/+ and Ctnnb1^fl(Ex3)/+p63^CreERT2/+ mice were castrated at eight weeks of age and injected with tamoxifen at age of 12 weeks. Then the mice were supplemented with androgen pellets. At the age of 16 weeks, mice were sacrificed, the prostates were harvested and implanted under the kidney capsule of SCID mice. Tissue grafts were isolated from SCID mice six weeks later (n=3). C. Histological analyses of prostate tissues isolated from Ctnnb1^fl(Ex3)/+p63^CreERT2/+ mice prior to kidney grafting. H&E stained sections of the (C1) AP, (C2) D/LP and (C3) VP. IHC staining of sequential section of prostatic tissues with antibodies for (C4) β-catenin, (C5) h-AR or (C6) Ck8 (brown). D. Histological analyses of prostate tissues isolated from R26hAR^L/+Ctnnb1^fl(Ex3)/+p63^CreERT2 mice prior to kidney grafting. H&E stained sections of the (D1) AP, (D2) D/LP or (D3) VP. IHC staining of sequential sections with (D4) β-catenin, (D5) h-AR or (D6) Ck8 antibodies (brown). E. Histological analyses of tissue grafts derived from Ctnnb1^fl(Ex3)/+p63^CreERT2 mice. H&E stained sections of graft tissues derived from the (E1) AP, (E2) D/LP or (E3) VP. IHC staining of sequential sections with (E4) β-catenin, (E5) h-AR or (E6) Ck8 antibodies (brown). F. Histological analyses of tissue grafts derived from R26hAR^L/+Ctnnb1^fl(Ex3)/+p63^CreERT2 mice. H&E stained sections of grafts derived from the (F1) AP, (F2) D/LP or (F3) VP. IHC staining of sequential sections with (F4) β-catenin, (F5) h-AR or (F6) Ck8 antibodies (brown).