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.