title: Androgens inhibit the proliferation of a variant of the human prostate cancer cell line LNCaP.
abstract: The paradoxical androgen response of R2, a subline of the human prostate cancer cell line LNCaP, is described here. Two androgens (DHT and R1881) decreased, in a dose-dependent manner, R2 cell proliferation and [3H]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 time and the percentage of G0-G1 cells. No evidence of androgen-induced apoptosis was found. Cloning allowed the selection of two cell populations on the basis of the response to 10 nM of R1881. Long term culture of uncloned R2 cells with R1881 modified reversibly the pattern of androgen response. R2 was compared to the androgen-stimulated LNCaP-FGC subline to investigate the causes of their different androgen responsiveness. The androgen receptor (number, affinity for hormones and antihormones, sedimentation constant and molecular weight) and androgen receptor genes (exon size and exon 8 sequence) were found to be identical in the two sublines. EGF stimulated LNCaP-FGC but not R2. Both cells were slightly stimulated by basic FGF but were insensitive to IGF-I and TGF beta 1.
  
  
  CONCLUSIONS
  (1) androgens inhibit the proliferation of R2 cells possibly by introducing a G0-G1 block; (2) this inhibition is incomplete because, at least in part, the R2 cell population is heterogeneous; (3) chronic androgen treatment induces reversible cell adaptation; and (4) there is no evidence that the loss of the classical stimulatory effect of androgen on cell proliferation and the gain of inhibitory effect are due to androgen receptor alteration or to a specific action of one of the four growth factors tested.
authors.affiliation: Institut National de la Santé et de la Recherche en Médecine, Université Claude Bernard Lyon I, France.
authors.forename: M O
authors.initials: MO
authors.lastname: Joly-Pharaboz
authors.forename: M C
authors.initials: MC
authors.lastname: Soave
authors.forename: B
authors.initials: B
authors.lastname: Nicolas
authors.forename: F
authors.initials: F
authors.lastname: Mebarki
authors.forename: M
authors.initials: M
authors.lastname: Renaud
authors.forename: O
authors.initials: O
authors.lastname: Foury
authors.forename: Y
authors.initials: Y
authors.lastname: Morel
authors.forename: J G
authors.initials: JG
authors.lastname: Andre
mesh_terms: D000595:Amino Acid Sequence; D000728:Androgens / Q000494:pharmacology*; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D004396:Coloring Agents; D004273:DNA, Neoplasm / Q000096:biosynthesis; D013196:Dihydrotestosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005091:Exons / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D008297:Male; D015741:Metribolone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000096:biosynthesis; D017354:Point Mutation / Q000235:genetics; D011471:Prostatic Neoplasms / Q000473:pathology*; D011944:Receptors, Androgen / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D045165:Testosterone Congeners / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
chemical_list: D000728:Androgens; D004396:Coloring Agents; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011944:Receptors, Androgen; D045165:Testosterone Congeners; D013778:Tetrazolium Salts; D013844:Thiazoles; D013196:Dihydrotestosterone; D016222:Fibroblast Growth Factor 2; D015741:Metribolone; D004815:Epidermal Growth Factor; C022616:thiazolyl blue