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Updated: Jun 1, 2026
Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses
Published on: October 24, 2019
The in-vitro response of 4 antisteroid receptor agents on the hormone-responsive prostate-cancer cell-line lncap
Abstract:
Previous reports indicate that flutamide withdrawal is associated with PSA declines and tumor shrinkage in selected patients with 'hormone-refractory' prostate cancer. Though the mechanisms underlying this effect are not clear, investigators have hypothesized that these effects are 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 the androgen receptor of LNCaP aberrantly recognizes a variety of steroids, including estrogen and progesterone, as androgenic agonists, there are no studies which examine the effect of estrogen antagonists and progesterone antagonist on baseline and androgen-stimulated LNCaP growth. In this report, LNCaP cells were cultured in phenol red-free media using charcoal-stripped sera. As previously reported, flutamide enhanced LNCaP growth and bicalutamide inhibited androgen-stimulated LNCaP proliferation. Neither tamoxifen nor RU486 influenced LNCaP growth (either in the presence or absence of exogenous androgens). From these data we conclude that antagonists of estrogen and progesterone action have no anti-proliferative effect on LNCaP cells and that the mutant androgen receptor expressed in these cells is quite restrictive in the recognition of compounds with antagonistic activity. The clinical implications of these findings are discussed.
Insights
Flutamide withdrawal may benefit hormone-refractory prostate cancer patients. However, estrogen and progesterone antagonists do not inhibit LNCaP cell growth, suggesting mutant androgen receptors are restrictive.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Flutamide withdrawal can lead to PSA declines and tumor shrinkage in hormone-refractory prostate cancer.
- Mutant androgen receptors (ARs) are hypothesized to mediate this effect by recognizing hydroxy-flutamide as an agonist.
- LNCaP cells possess mutant ARs that recognize various steroids, but the effect of estrogen/progesterone antagonists on these cells is unknown.
Purpose of the Study:
- To investigate the anti-proliferative effects of estrogen and progesterone antagonists on LNCaP cells.
- To determine if tamoxifen or RU486 influence baseline or androgen-stimulated LNCaP cell growth.
Main Methods:
- LNCaP cells were cultured in phenol red-free media with charcoal-stripped sera.
- Cells were treated with tamoxifen or RU486 in the presence or absence of exogenous androgens.
- Cell growth was assessed to evaluate the effects of the antagonists.
Main Results:
- Flutamide enhanced LNCaP cell growth, consistent with previous findings.
- Bicalutamide inhibited androgen-stimulated LNCaP proliferation.
- Neither tamoxifen nor RU486 affected LNCaP cell growth under any tested condition.
Conclusions:
- Antagonists of estrogen and progesterone action do not exhibit anti-proliferative effects on LNCaP cells.
- The mutant androgen receptor in LNCaP cells demonstrates restrictive recognition of compounds with antagonistic activity.
- These findings suggest limitations in targeting estrogen or progesterone pathways in prostate cancers with specific mutant ARs.
