Insulin-like growth factor II and androgen receptor expression in the prostate

Objective To determine the effect of insulin-like growth factor (IGF)-II on androgen receptor (AR) expression in prostate tissue, as IGFs may be impor tant in re-activating androgen-regulated genes in advanced prostate cancer because they can trans-activate the AR in the absence of ligand. Materials and methods Primary BPH stromal cells, LNCaP and U2OS cells were grown in full medium, medium devoid of growth factors and devoid medium sup plemented with IGF-II. The relationship between IGF-II and AR expression wa s then investigated using the reverse-transcription polymerase chain reacti on, and the effects of anti-androgens on IGF-II expression assessed using n orthern blot analysis. Results IGF-II had no effect in benign tissue, but the AR expression double d in LNCaP and U2OS cells after culture with IGF-II. Androgens had a minima l effect on IGF-II mRNA levels, but anti-androgens reduced IGF-II mRNA leve ls by more than half. Conclusion These findings support the idea of a complementary paracrine (IG F) and autocrine (androgen) growth loop in prostate tissue. The study sugge sts that IGF-II has a role in regulating AR expression in prostate cancer c ells, and that the action of anti-androgens is mediated partly by an abilit y to suppress IGF-II expression.