THE IN-VITRO RESPONSE OF 4 ANTISTEROID RECEPTOR AGENTS ON THE HORMONE-RESPONSIVE PROSTATE-CANCER CELL-LINE LNCAP

Previous reports indicate that flutamide withdrawal is associated with PSA declines and tumor shrinkage in selected patients with 'hormone-r efractory' prostate cancer. Though the mechanisms underlying this effe ct are not clear, investigators have hypothesized that these effects a re mediated by mutant androgen receptors recognizing hydroxy-flutamide as an androgenic agonist. Such receptors have been well described in the human prostate cancer cell line LNCaP. Despite the finding that th e androgen receptor of LNCaP aberrantly recognizes a variety of steroi ds, including estrogen and progesterone, as androgenic agonists, there are no studies which examine the effect of estrogen antagonists and p rogesterone antagonist on baseline and androgen-stimulated LNCaP growt h. In this report, LNCaP cells were cultured in phenol red-free media using charcoal-stripped sera. As previously reported, flutamide enhanc ed LNCaP growth and bicalutamide inhibited androgen-stimulated LNCaP p roliferation. Neither tamoxifen nor RU486 influenced LNCaP growth (eit her in the presence or absence of exogenous androgens). From these dat a we conclude that antagonists of estrogen and progesterone action hav e no anti-proliferative effect on LNCaP cells and that the mutant andr ogen receptor expressed in these cells is quite restrictive in the rec ognition of compounds with antagonistic activity. The clinical implica tions of these findings are discussed.