help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhao, X.-Y.
Right arrow Articles by Feldman, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhao, X.-Y.
Right arrow Articles by Feldman, D.
Endocrinology Vol. 138, No. 8 3290-3298
Copyright © 1997 by The Endocrine Society

ARTICLES

1{alpha},25-Dihydroxyvitamin D3 Actions in LNCaP Human Prostate Cancer Cells Are Androgen-Dependent1

Xiao-Yan Zhao, Lan H. Ly, Donna M. Peehl and David Feldman

Departments of Medicine and Urology (D.M.P.), Stanford University School of Medicine, Stanford, California 94305

Address all correspondence and requests for reprints to: David Feldman, M.D., Division of Endocrinology, Gerontology and Metabolism, Stanford University Medical Center, Room S005, Stanford, California 94305-5103. E-mail address: feldman{at}cmgm.stanford.edu

We and others have recently shown that 1{alpha},25-dihydroxyvitamin D3 [1,25-(OH)2D3] significantly inhibits cell proliferation and increases secretion of prostate-specific antigen (PSA) in LNCaP cells, an androgen-responsive human prostate cancer cell line. The present study was designed to investigate the possible interactions between 1,25-(OH)2D3 and androgens in the regulation of LNCaP cellular function. LNCaP cell growth was dose-dependently inhibited by 1,25-(OH)2D3 (60% inhibition at 10 nM) when cells were cultured in medium supplemented with FBS (FBS medium). 1,25-(OH)2D3-treated cells showed a 5-fold increase in PSA secretion, similar to the increase seen in dihydrotestosterone (DHT)-treated cells. In combination, 1,25-(OH)2D3 and DHT synergistically enhanced PSA secretion 22-fold. This synergistic effect was even greater when cells were cultured in medium supplemented with charcoal-stripped serum (CSS medium), where endogenous steroids are substantially depleted. Under these conditions, 1,25-(OH)2D3 and DHT together stimulated PSA secretion up to 50-fold over the untreated control. Radioligand binding assays and Western blot analyses showed that the androgen receptor (AR) content was increased significantly by 1,25-(OH)2D3 at 48 h. Furthermore, the steady-state mRNA level of AR was up-regulated approximately 2-fold by 1,25-(OH)2D3 at 24 h. When cells were grown in CSS medium, 1,25-(OH)2D3 alone no longer inhibited cell growth or induced PSA secretion. Titration experiments revealed that the addition of DHT at 1 nM to the medium restored the antiproliferative activity of 1,25-(OH)2D3. Conversely, an antiandrogen, Casodex, completely blocked 1,25-(OH)2D3 antiproliferative and PSA stimulation activities when cells were cultured in FBS medium. In conclusion, these results demonstrate that the antiproliferative and PSA induction activities of 1,25-(OH)2D3 in LNCaP cells are dependent upon androgen action and that AR up-regulation by 1,25-(OH)2D3 likely contributes to the synergistic actions of 1,25-(OH)2D3 and DHT in these cells.




This article has been cited by other articles:


Home page
 Molecular Cancer TherapeuticsHome page
J. Kaeding, J. Belanger, P. Caron, M. Verreault, A. Belanger, and O. Barbier
Calcitrol (1{alpha},25-dihydroxyvitamin D3) inhibits androgen glucuronidation in prostate cancer cells
Mol. Cancer Ther., February 1, 2008; 7(2): 380 - 390.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
H.-J. Ting, B.-Y. Bao, J. E. Reeder, E. M. Messing, and Y.-F. Lee
Increased Expression of Corepressors in Aggressive Androgen-Independent Prostate Cancer Cells Results in Loss of 1{alpha},25-Dihydroxyvitamin D3 Responsiveness
Mol. Cancer Res., September 1, 2007; 5(9): 967 - 980.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. Peng, P. J. Malloy, J. Wang, and D. Feldman
Growth Inhibitory Concentrations of Androgens Up-Regulate Insulin-Like Growth Factor Binding Protein-3 Expression via an Androgen Response Element in LNCaP Human Prostate Cancer Cells
Endocrinology, October 1, 2006; 147(10): 4599 - 4607.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
S. Nagpal, S. Na, and R. Rathnachalam
Noncalcemic Actions of Vitamin D Receptor Ligands
Endocr. Rev., August 1, 2005; 26(5): 662 - 687.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
L. V. Stewart and N. L. Weigel
Vitamin D and Prostate Cancer
Experimental Biology and Medicine, April 1, 2004; 229(4): 277 - 284.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. Crescioli, P. Ferruzzi, A. Caporali, R. Mancina, A. Comerci, M. Muratori, M. Scaltriti, G. B. Vannelli, S. Smiroldo, R. Mariani, et al.
Inhibition of Spontaneous and Androgen-Induced Prostate Growth by a Nonhypercalcemic Calcitriol Analog
Endocrinology, July 1, 2003; 144(7): 3046 - 3057.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
A. J. James, I. U. Agoulnik, J. M. Harris, G. Buchanan, W. D. Tilley, M. Marcelli, D. J. Lamb, and N. L. Weigel
A Novel Androgen Receptor Mutant, A748T, Exhibits Hormone Concentration-Dependent Defects in Nuclear Accumulation and Activity Despite Normal Hormone-Binding Affinity
Mol. Endocrinol., December 1, 2002; 16(12): 2692 - 2705.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C.-L. Hsieh, L. Yang, L. Miao, F. Yeung, C. Kao, H. Yang, H. E. Zhau, and L. W. K. Chung
A Novel Targeting Modality to Enhance Adenoviral Replication by Vitamin D3 in Androgen-independent Human Prostate Cancer Cells and Tumors
Cancer Res., June 1, 2002; 62(11): 3084 - 3092.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. V. Krishnan, X.-Y. Zhao, S. Swami, L. Brive, D. M. Peehl, K. R. Ely, and D. Feldman
A Glucocorticoid-Responsive Mutant Androgen Receptor Exhibits Unique Ligand Specificity: Therapeutic Implications for Androgen-Independent Prostate Cancer
Endocrinology, May 1, 2002; 143(5): 1889 - 1900.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. A. Moffatt, W. U. Johannes, T. E. Hedlund, and G. J. Miller
Growth Inhibitory Effects of 1{alpha}, 25-Dihydroxyvitamin D3 Are Mediated by Increased Levels of p21 in the Prostatic Carcinoma Cell Line ALVA-31
Cancer Res., October 1, 2001; 61(19): 7122 - 7129.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
S. C. Dixon, K. B. Knopf, and W. D. Figg
The Control of Prostate-Specific Antigen Expression and Gene Regulation by Pharmacological Agents
Pharmacol. Rev., March 1, 2001; 53(1): 73 - 92.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. D. Sadar and M. E. Gleave
Ligand-independent Activation of the Androgen Receptor by the Differentiation Agent Butyrate in Human Prostate Cancer Cells
Cancer Res., October 1, 2000; 60(20): 5825 - 5831.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
J. L. Martin and S. L. Pattison
Insulin-Like Growth Factor Binding Protein-3 Is Regulated by Dihydrotestosterone and Stimulates Deoxyribonucleic Acid Synthesis and Cell Proliferation in LNCaP Prostate Carcinoma Cells
Endocrinology, July 1, 2000; 141(7): 2401 - 2409.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
X.-Y. Zhao, D. M. Peehl, N. M. Navone, and D. Feldman
1{alpha},25-Dihydroxyvitamin D3 Inhibits Prostate Cancer Cell Growth by Androgen-Dependent and Androgen-Independent Mechanisms
Endocrinology, July 1, 2000; 141(7): 2548 - 2556.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. R. Qadan, C. M. Perez-Stable, R. H. Schwall, K. L. Burnstein, R. C. Ostenson, G. A. Howard, and B. A. Roos
Hepatocyte Growth Factor and Vitamin D Cooperatively Inhibit Androgen-Unresponsive Prostate Cancer Cell Lines
Endocrinology, July 1, 2000; 141(7): 2567 - 2573.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. E. Blutt, T. J. McDonnell, T. C. Polek, and N. L. Weigel
Calcitriol-Induced Apoptosis in LNCaP Cells Is Blocked By Overexpression of Bcl-2
Endocrinology, January 1, 2000; 141(1): 10 - 17.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. H. Ly, X.-Y. Zhao, L. Holloway, and D. Feldman
Liarozole Acts Synergistically with 1{alpha},25-Dihydroxyvitamin D3 to Inhibit Growth of DU 145 Human Prostate Cancer Cells by Blocking 24-Hydroxylase Activity
Endocrinology, May 1, 1999; 140(5): 2071 - 2076.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
X.-Y. Zhao, L. H. Ly, D. M. Peehl, and D. Feldman
Induction of Androgen Receptor by 1{alpha},25-Dihydroxyvitamin D3 and 9-cis Retinoic Acid in LNCaP Human Prostate Cancer Cells
Endocrinology, March 1, 1999; 140(3): 1205 - 1212.
[Abstract] [Full Text]

Home page
 Mol. Endocrinol.Home page
J. M. Kokontis, N. Hay, and S. Liao
Progression of LNCaP Prostate Tumor Cells during Androgen Deprivation: Hormone-Independent Growth, Repression of Proliferation by Androgen, and Role for p27Kip1 in Androgen-Induced Cell Cycle Arrest
Mol. Endocrinol., July 1, 1998; 12(7): 941 - 953.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1997 by The Endocrine Society