Proposed model of p53 regulation of IGF1R gene expression. Tumor suppressor p53 is a negative cell cycle regulator that prevents passage of damaged DNA to daughter cells. Wild type p53 suppresses IGF1R gene transcription, leading to reduced IGF1R levels and a decrease in IGF1- and IGF2-stimulated IGF1R phosphorylation. As a net result, cell proliferation is reduced and apoptosis is increased (left panel). Loss-of-function or gain-of-function mutations of p53 are common events in cancer (right panel). Mutant forms of p53 are able to transactivate the IGF1R gene, with ensuing increase in IGF1R biosynthesis. Augmented IGF1R expression and activation is a pre-requisite for tumor growth and is usually associated with abrogation of apoptosis (i.e., enhanced cell survival). A similar paradigm applies for BRCA1.