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Insulin-like growth factor II and androgen receptor expression in the prostate
V J Gnanapragasam1, P J McCahy, D E Neal
1School of Surgical and Reproductive Sciences, Medical School, University of Newcastle upon Tyne, UK.
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 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 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.