• castration-resistance;
  • fibroblast growth factor signaling;
  • stem cells;
  • tumor suppression;
  • tyrosine kinases



Despite dramatic positive effects, there is evidence that the androgen receptor (AR) may negatively influence prostate tumor progression. Understanding the AR repressor function and how it is subverted is of particular importance in anti-androgen and AR intervention strategies.


AR, resident FGFR2IIIb, and ectopic FGFR1 were expressed by transfection in the AR-negative epithelial cell line DTE that predominates in cell culture of AR-positive androgen-responsive model Dunning R3327 rat prostate tumors. Androgen-responsiveness at transcription was measured by a luciferase reporter. Cell population growth rates were assessed by cell counts, DNA synthesis, and expression of cell cycle genes. AR variants (ARVs) were assessed by immunochemistry and nuclease protection of mRNA.


Expression of AR inhibited cell population growth of AR-negative DTE cells at the G1–S phase of the cell cycle. Ectopic FGFR1, but not resident FGFR2IIIb abrogated the growth inhibitory effects of AR. Appearance of ARVs was coincident with co-expression of FGFR1 and AR and abrogation of the AR-dependent inhibition of cell growth.


DTE cells may represent non-malignant AR-negative progenitors whose population is restricted by activation of AR in vivo. Ectopic expression of epithelial FGFR1, a common observation in tumors, overrides the inhibition of AR and thus may contribute to evolution of androgen and AR independent tumors. These results are consistent with the notion that some tumor cells are negatively restricted by AR and are unleased by androgen-deprivation or ectopic expression of FGFR1. ARV's may play a role in the bypass of the negative restrictions of AR. Prostate 71:1691–1700, 2011. © 2011 Wiley-Liss, Inc.