AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Translational Res 2010;2(2):200-208

Original Article
Androgen mediated translational and postranslational regulation of
IGFBP-2 in androgen-sensitive LNCaP human prostate cancer cells

David J. DeGraff, Adam A. Aguiar, Qian Chen, Lisa K. Adams, B. Jill Williams, Robert A. Sikes

Laboratory for Cancer Ontogeny and Therapeutics, Department of Biological Sciences, University of Delaware,
Newark, DE; Center for Translational Cancer Research, University of Delaware, Newark, DE; Department of
Urology, Louisiana State University Health Sciences Center, Shreveport, LA.

Received February 24, 2010; accepted March, 2010; available online March, 2010

Abstract: The insulin-like growth factor (IGF) axis is associated intimately with prostate cancer (PCa) cell
development, growth, survival and metastasis. In particular, increased levels of IGFBP-2 expression are
associated with advanced PCa, bone metastasis, and the development of castrate resistant PCa. Previously, we
reported that androgen treatment decreased intracellular and extracellular IGFBP-2 in the androgen sensitive (AS)
PCa cell line, LNCaP. Nonetheless, the mechanism by which androgen treatment decreases expression of
IGFBP-2 is not clear. Since elevated IGFBP-2 is associated with a variety of advanced cancers, including PCa,
coupled with the fact that hormone ablation is the customary treatment modality for advanced PCa, a complete
understanding of the influence of androgens on IGFBP-2 expression is essential. Androgen treatment initially
increased steady state IGFBP-2 mRNA levels in LNCaP cells. Extended androgen treatment on LNCaP resulted
in a time-dependent decrease in both steady state IGFBP-2 mRNA and protein. Polysomal mRNA analysis
showed no difference in IGFBP-2 association with a given fraction; however, Q-PCR revealed less IGFBP-2
mRNA in each androgen-treated fraction. In addition there was an overall decrease in polysome mRNA after
androgen treatment. The decrease in intracellular IGFBP-2 was found to be, at least in part, proteasome
dependent while the extracellular proteolysis of IGFBP-2 was prevented in the presence of serine protease
inhibitors. These data indicate that androgen acts via multiple levels to down-regulate IGFBP-2 in LNCaP PCa
cells. (AJTR1002004).

Key words: Serine protease, proteasome, growth factor, prostate cancer, regulation, high-density culture,
androgen, insulin-like growth factor binding protein

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Address all correspondence to:
Robert A. Sikes, PhD
Director, Center for Translational Cancer Research
Laboratory for Cancer Ontogeny and Therapeutics
Department of Biological Sciences
University of Delaware
Newark, DE 19716, USA.