Fig. 7.

Constitutively active NF-κB results in xenograft maintenance under castrated conditions. (A) Treatment schema for Athymic Nude-Foxn1nu mice. NHPrE1-EV (empty vector control), NHPrE1-EE (constitutively active NF-κB), and NHPrE1-AR-V7 (overexpressing AR-V7) cells were recombined with rat urogenital sinus mesenchyme and grafted under the kidney capsule of mice. All mice were castrated and supplemented with testosterone (T) pellets for 2 weeks after grafting. After 2 weeks mice were separated into two groups. Group 1 (n = 9 mice) had a replacement T pellet and Group 2 (n = 9 mice) had their T pellet removed. Growth was assessed after 6 weeks and mice were euthanized. (B) Representative H&E images of recombinants containing NHPrE-EV, NHPrE1-EE, and NHPrE1-AR-V7 cells. Under continuous androgenic stimulation these show glandular epithelial structures that had developed. Following castration the NHPrE1-EV and NHPrE1-AR-V7 containing grafts, contain residual epithelium but no obvious retention of glandular structure, consistent with post castration regression in a recombinant. In contrast NHPrE1-EE grafts show a maintenance of glandular architecture, representing protection from regression in the face of androgen ablation.