Finally, when Pr111 PIN cells were stimulated with recombinant Spp1, inhibition of activated Akt and/or JNK by Wortmannin and/or SP600125 completely abolished Pr111 cell proliferation (Figure 5B), indicating that macrophage Spp1 induces PIN cell proliferation through activation of Akt and JNK signaling. The gene discussed is SPP1; the disease is prostate intraepithelial neoplasia.