Although Pten heterozygosity per se results in low-grade PIN in mice [151], Schutzman et al. [140] showed that concomitant inactivation of the Sprouty genes (Spry1 and Spry2) accelerated emergence of PIN and promoted development of more extensive, high-grade phenotype along with the transition to invasive cancer. This evidence concerns the gene SPRY1 and prostate intraepithelial neoplasia.