In a preclinical mouse model, inactivation of Rb alone only led to PIN (prostatic intraepithelial neoplasia) formation and concurrent deletion of Tp53 was required for the development of metastatic carcinoma with neuroendocrine features [56], suggesting TP53 loss may be a prerequisite for functions mediated by RB1 loss. This evidence concerns the gene TP53 and prostate intraepithelial neoplasia.