This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Martin, J. L. Articles by Pattison, S. L. Search for Related Content PubMed PubMed Citation Articles by Martin, J. L. Articles by Pattison, S. L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Prostate Cancer

Insulin-Like Growth Factor Binding Protein-3 Is Regulated by Dihydrotestosterone and Stimulates Deoxyribonucleic Acid Synthesis and Cell Proliferation in LNCaP Prostate Carcinoma Cells¹

Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia

Address all correspondence and requests for reprints to: Dr. Janet Martin, Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, University of Sydney, New South Wales, 2065 Australia. E-mail: janetlm{at}med.usyd.edu.au

We have investigated the production and actions of a growth regulatory protein, insulin-like growth factor binding protein (IGFBP)-3, in the androgen-responsive prostate carcinoma cell line LNCaP. Confluent monolayers of cells secreted approximately 0.7 ng/ml IGFBP-3 over 24 h. Dihydrotestosterone (DHT, 10 nM) and 1,25-dihydroxyvitamin D₃ (vitamin D, 10 nM) increased IGFBP-3 in media to 149 ± 15% and 206 ± 18% of control, respectively, when added separately, and to 453 ± 28% of control when used in combination. IGFBP-2, secreted at approximately 25-fold higher concentrations than IGFBP-3, was increased 50% by 10 nM DHT, but there was no effect of vitamin D on IGFBP-2 production in the absence or presence of DHT. Cell-associated IGFBP-3, and immunoreactive IGFBP-3 species of 20 kDa and 30 kDa were also increased in response to vitamin D plus DHT. A combination of vitamin D and DHT increased DNA synthesis in LNCaP cells 3-fold, and this was at least partly mediated by endogenous IGFBP-3 because anti-IGFBP-3 IgG, but not nonimmune serum IgG, reduced the stimulatory effect of vitamin D and DHT from 293 ± 11.6% to 161 ± 30.7% of control levels (P < 0.0001). Basal and DHT plus vitamin D-stimulated thymidine incorporation was significantly increased by 50 ng/ml human plasma-derived purified IGFBP-3. After 4 days treatment with vitamin D plus DHT, or pure IGFBP-3, LNCaP cell numbers were increased relative to control. These results indicate a role for IGFBP-3 in the proliferation of androgen-responsive prostate carcinoma cells.

This article has been cited by other articles:

				J. L. Martin and R. C. Baxter Expression of Insulin-Like Growth Factor Binding Protein-2 by MCF-7 Breast Cancer Cells Is Regulated through the Phosphatidylinositol 3-Kinase/AKT/Mammalian Target of Rapamycin Pathway Endocrinology, May 1, 2007; 148(5): 2532 - 2541. [Abstract] [Full Text] [PDF]

				S. Seenundun and B. Robaire Time-Dependent Rescue of Gene Expression by Androgens in the Mouse Proximal Caput Epididymidis-1 Cell Line after Androgen Withdrawal Endocrinology, January 1, 2007; 148(1): 173 - 188. [Abstract] [Full Text] [PDF]

				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]

				C. Burrows, J. M. P. Holly, N. J. Laurence, E. G. Vernon, J. V. Carter, M. A. Clark, J. McIntosh, C. McCaig, Z. E. Winters, and C. M. Perks Insulin-Like Growth Factor Binding Protein 3 Has Opposing Actions on Malignant and Nonmalignant Breast Epithelial Cells that Are Each Reversible and Dependent upon Cholesterol-Stabilized Integrin Receptor Complexes Endocrinology, July 1, 2006; 147(7): 3484 - 3500. [Abstract] [Full Text] [PDF]

				K. V. Desai, A. M. Michalowska, P. Kondaiah, J. M. Ward, J. H. Shih, and J. E. Green Gene Expression Profiling Identifies a Unique Androgen-Mediated Inflammatory/Immune Signature and a PTEN (Phosphatase and Tensin Homolog Deleted on Chromosome 10)-Mediated Apoptotic Response Specific to the Rat Ventral Prostate Mol. Endocrinol., December 1, 2004; 18(12): 2895 - 2907. [Abstract] [Full Text] [PDF]

				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]

				H. Yu, X.-O. Shu, B. D. L. Li, Q. Dai, Y.-T. Gao, F. Jin, and W. Zheng Joint Effect of Insulin-like Growth Factors and Sex Steroids on Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., October 1, 2003; 12(10): 1067 - 1073. [Abstract] [Full Text] [PDF]

				J. L. Martin, S. M. Weenink, and R. C. Baxter Insulin-like Growth Factor-binding Protein-3 Potentiates Epidermal Growth Factor Action in MCF-10A Mammary Epithelial Cells. INVOLVEMENT OF p44/42 AND p38 MITOGEN-ACTIVATED PROTEIN KINASES J. Biol. Chem., January 24, 2003; 278(5): 2969 - 2976. [Abstract] [Full Text] [PDF]

				A. Hoeflich, R. Reisinger, H. Lahm, W. Kiess, W. F. Blum, H. J. Kolb, M. M. Weber, and E. Wolf Insulin-like Growth Factor-binding Protein 2 in Tumorigenesis: Protector or Promoter? Cancer Res., December 1, 2001; 61(24): 8601 - 8610. [Full Text] [PDF]

				G. A. BROCKMANN, C. S. HALEY, E. WOLF, S. KARLE, J. KRATZSCH, U. RENNE, M. SCHWERIN, and A. HOEFLICH Genome-wide search for loci controlling serum IGF binding protein levels of mice FASEB J, April 1, 2001; 15(6): 978 - 987. [Abstract] [Full Text] [PDF]