However, two transgenic PC models with Akt activation plus Rb loss exhibited different metastatic development: Pten/RbPE:−/− mice produced systemic metastatic adenocarcinomas with high AKT2 activation, whereas RbPE:−/− mice deficient for the Src-scaffolding protein, Akap12, induced high-grade prostatic intraepithelial neoplasias and indolent lymph node dissemination, correlating with upregulated phosphotyrosyl PI3K-p85α. The gene discussed is PIK3CA; the disease is pachyonychia congenita.