Androgen receptor expression induces FGF2, FGF-binding protein production, and FGF2 release in prostate carcinoma cells: role of FGF2 in growth, survival, and androgen receptor down-modulation.

BACKGROUND
Alterations in fibroblast growth factors (FGFs) production and/or FGF
receptors expression have been described to play key roles in prostate
tumor progression, particularly in androgen-independent tumors. However,
the role of androgen receptor (AR) in altering FGF-mediated growth and
survival of prostatic neoplastic cells has not been completely defined.
In this study, we investigated the alterations in FGF2 production and
utilization by the PC3 cell line, after transfection with a full-length
AR.

METHODS
FGF1,2,7, FGF-binding protein (FGF-BP) production and FGF receptor (FGFR)
1-4 expression were investigated by polymerase chain reaction (PCR) and
Western blot analysis.

RESULTS
De novo AR expression by PC3 cells restores FGFR2 IIIb isoform expression
and sensitivity to FGF7 and FGF2. Androgen stimulation induces AR+ PC3
clones to secrete FGF-BP, likely responsible for activation and
mobilization from the extracellular matrix of the high amounts of FGF2
produced by the same cells. In addition to the effects on cell
proliferation, FGF2 maintains the survival of AR+ PC3 clones through a
positive modulation of the Bcl-2 protein and down-modulates AR protein
expression, allowing the escape of selected clones from androgen
regulation.

CONCLUSION
In the presence of an active AR, the combined production of FGF2 and FGF-
BP may play an important role in the progression of prostate cancer
through the selection of AR- clones expressing high levels of Bcl-2.
Prostate 53: 310-321, 2002. © 2002 Wiley-Liss, Inc.