ANDROGENS INHIBIT THE PROLIFERATION OF A VARIANT OF THE HUMAN PROSTATE-CANCER CELL-LINE LNCAP

The paradoxical androgen response of R2, a subline of the human prosta te cancer cell line LNCaP, is described here. Two androgens (DHT and R 1881) decreased, in a dose-dependent manner, R2 cell proliferation and [H-3]thymidine incorporation. These ligand and cell specific effects were accompanied by an increase in the metabolism of the vital dye MTT and in cell protein content. Both androgens increased the doubling ti me and the percentage of G(0)-G(1) cells. No evidence of androgen-indu ced apoptosis was found. Cloning allowed the selection of two cell pop ulations on the basis of the response to 10 nM of R1881. Long term cul ture of uncloned R2 cells with R1881 modified reversibly the pattern o f androgen response. R2 was compared to the androgen-stimulated LNCaP- FGC subline to investigate the causes of their different androgen resp onsiveness. The androgen receptor (number, affinity for hormones and a ntihormones, sedimentation constant and molecular weight) and androgen receptor genes (exon size and exon 8 sequence) were found to be ident ical in the two sublines. EGF stimulated LNCaP-FGC but not R2. Both ce lls were slightly stimulated by basic FGF but were insensitive to IGF- I and TGF beta 1. In conclusion: (1) androgens inhibit the proliferati on of R2 cells possibly by introducing a G(0)-G(1) block; (2) this inh ibition is incomplete because, at least in part, the R2 cell populatio n is heterogeneous; (3) chronic androgen treatment induces reversible cell adaptation; and (4) there is no evidence that the loss of the cla ssical stimulatory effect of androgen on cell proliferation and the ga in of inhibitory effect are due to androgen receptor alteration or to a specific action of one of the four growth factors tested.