Prostatic inflammation is of considerable importance to urologic research because of its association with benign prostatic hyperplasia and prostate cancer. However, the mechanisms by which inflammation leads to proliferation and growth remain obscure. Here, we show that insulin-like growth factors (IGFs), previously known as critical developmental growth factors during prostate organogenesis, are induced by inflammation as part of the proliferative recovery to inflammation. Using genetic models and in vivo IGF receptor blockade, we demonstrate that the hyperplastic response to inflammation depends on interleukin-1-driven IGF signaling. We show that human prostatic hyperplasia is associated with IGF pathway activation specifically localized to foci of inflammation. This demonstrates that mechanisms of inflammation-induced epithelial proliferation and hyperplasia involve the induction of developmental growth factors, further establishing a link between inflammatory and developmental signals and providing a mechanistic basis for the management of proliferative diseases by IGF pathway modulation.

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PCa (12) and HGPIN with BPH (5) revealed concordant methylation pattern. Among T3-PCa a gradual loss of methylation with increasing dedifferentiation was observed (80% in G2 vs. 44% in G3).CONCLUSIONS: Silenced myopodin gene was inducible with TSA and with combined treatment with TSA and 5-aza-dC. These results indicate that epigenetic histone and DNA modifications are involved in PCa associated myopodin inactivation. Partial methylation of myopodin may indicate at histological dedifferentiation in advanced PCa.Source of Funding: This study was supported by grants