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 important in reactivating 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 supplemented with IGF-II. The relationship between IGF-II and AR expression was then investigated using the reverse-transcription polymerase chain reaction, and the effects of anti-androgens on IGF-II expression assessed using northern blot analysis. Results: IGF-II had no effect in benign tissue, but the AR expression doubled in LNCaP and U2OS cells after culture with IGF-II. Androgens had a minimal effect on IGF-II mRNA levels, but anti-androgens reduced IGF-II mRNA levels by more than half. Conclusion: These findings support the idea of a complementary paracrine (IGF) and autocrine (androgen) growth loop in prostate tissue. The study suggests that IGF-II has a role in regulating AR expression in prostate cancer cells, and that the action of anti-androgens is mediated partly by an ability to suppress IGF-II expression.