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

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The insulin-like growth factor (IGF) axis is associated intimately with prostate cancer (PCa) 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. 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.

Original languageEnglish (US)
Pages (from-to)200-208
Number of pages9
JournalAmerican Journal of Translational Research
Volume2
Issue number2
StatePublished - Jun 4 2010

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Clinical Biochemistry
  • Cancer Research

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