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).
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. E-mail: email@example.com