Vitamin D analogues have an antiproliferative effect on prostate cancer cells in vitro and thus have been proposed as candidates for chemoprevention of prostate cancer. Insulin-like growth factor (IGF)-I has been shown to protect cells from apoptosis and plays an essential role in normal prostate physiology. We have studied the effects of the 1,25-dihydroxyvitamin D3 analogue EB1089 on the IGF system in the prostate in vivo. Treatment of rats with EB1089 for 14 days caused a 25% decrease in ventral prostate weight. Apoptosis was detected in prostate sections of EB1089-treated rats by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay and histologic examination of hematoxylin/eosin stained tissue sections indicated that secretory epithelial cells were flattened, a characteristic of cells undergoing pressure-induced atrophy. Ventral prostate regression was associated with 15- to 25-fold increases in gene expression of IGF-binding proteins (IGFBPs)-2,-3,-4 and -5. We also observed a 40-fold increase in prostatic IGF-I mRNA levels in response to EB1089. Although we have previously shown that castration of rats leads to upregulation of IGFBPs in the ventral prostate, EB1089 treatment had no effect on serum levels of dihydrotestosterone or free testosterone. These results suggest that prostate regression induced by EB1089 may be related to alterations in availability of IGF-I as a result of increased production of IGFBPs.

This article has been cited by other articles:

				R. P Singh and R. Agarwal Mechanisms of action of novel agents for prostate cancer chemoprevention. Endocr. Relat. Cancer, September 1, 2006; 13(3): 751 - 778. [Abstract] [Full Text] [PDF]

				M. F. McCarty Targeting Multiple Signaling Pathways as a Strategy for Managing Prostate Cancer: Multifocal Signal Modulation Therapy Integr Cancer Ther, December 1, 2004; 3(4): 349 - 380. [Abstract] [PDF]

				P. Yin, Q. Xu, and C. Duan Paradoxical Actions of Endogenous and Exogenous Insulin-like Growth Factor-binding Protein-5 Revealed by RNA Interference Analysis J. Biol. Chem., July 30, 2004; 279(31): 32660 - 32666. [Abstract] [Full Text] [PDF]

				R. J. Wood, L. Tchack, G. Angelo, R. E. Pratt, and L. A. Sonna DNA microarray analysis of vitamin D-induced gene expression in a human colon carcinoma cell line Physiol Genomics, April 13, 2004; 17(2): 122 - 129. [Abstract] [Full Text] [PDF]

				C. A. Heinlein and C. Chang Androgen Receptor in Prostate Cancer Endocr. Rev., April 1, 2004; 25(2): 276 - 308. [Abstract] [Full Text] [PDF]

				D. M. Peehl, A. V. Krishnan, and D. Feldman Pathways Mediating the Growth-Inhibitory Actions of Vitamin D in Prostate Cancer J. Nutr., July 1, 2003; 133(7): 2461S - 2469. [Abstract] [Full Text] [PDF]

				F. Galbiati, L. Polastri, B. Thorens, P. Dupraz, P. Fiorina, U. Cavallaro, G. Christofori, and A. M. Davalli Molecular Pathways Involved in the Antineoplastic Effects of Calcitriol on Insulinoma Cells Endocrinology, May 1, 2003; 144(5): 1832 - 1841. [Abstract] [Full Text] [PDF]

				S. M. Firth and R. C. Baxter Cellular Actions of the Insulin-Like Growth Factor Binding Proteins Endocr. Rev., December 1, 2002; 23(6): 824 - 854. [Abstract] [Full Text] [PDF]

				A. P. Chokkalingam, K. A. McGlynn, Y.-T. Gao, M. Pollak, J. Deng, I. A. Sesterhenn, F. K. Mostofi, J. F. Fraumeni Jr., and A. W. Hsing Vitamin D Receptor Gene Polymorphisms, Insulin-like Growth Factors, and Prostate Cancer Risk: A Population-based Case-Control Study in China Cancer Res., June 1, 2001; 61(11): 4333 - 4336. [Abstract] [Full Text] [PDF]

				J. Prudencio, N. Akutsu, N. Benlimame, T. Wang, Y. Bastien, R. Lin, M. J. Black, M. A. Alaoui-Jamali, and J. H. White Action of Low Calcemic 1{{alpha}},25-Dihydroxyvitamin D3 Analogue EB1089 in Head and Neck Squamous Cell Carcinoma J Natl Cancer Inst, May 16, 2001; 93(10): 745 - 753. [Abstract] [Full Text] [PDF]

				R. H. Drivdahl, C. Sprenger, K. Trimm, and S. R. Plymate Inhibition of Growth and Increased Expression of Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) and -6 in Prostate Cancer Cells Stably Transfected with Antisense IGFBP-4 Complementary Deoxyribonucleic Acid Endocrinology, May 1, 2001; 142(5): 1990 - 1998. [Abstract] [Full Text]

				C. Deal, J. Ma, F. Wilkin, J. Paquette, F. Rozen, B. Ge, T. Hudson, M. Stampfer, and M. Pollak Novel Promoter Polymorphism in Insulin-Like Growth Factor-Binding Protein-3: Correlation with Serum Levels and Interaction with Known Regulators J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1274 - 1280. [Abstract] [Full Text]

				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]

				A. J. Butt, S. M. Firth, M. A. King, and R. C. Baxter Insulin-like Growth Factor-binding Protein-3 Modulates Expression of Bax and Bcl-2 and Potentiates p53-independent Radiation-induced Apoptosis in Human Breast Cancer Cells J. Biol. Chem., December 8, 2000; 275(50): 39174 - 39181. [Abstract] [Full Text] [PDF]