Our data indicate that: (1) activation of p53 is negatively regulated by IGF1R, as indicated by the augmented phosphorylation of p53 in IGF1R-KD cells; (2) p53 directly binds to the INSR promoter region in cells with a disrupted IGF1R; (3) wild-type p53 represses INSR promoter activity in IGF1R-KD and INSR-KD cells, while enhancing promoter activity in control cells; (4) mutant p53 stimulates INSR promoter activity in breast cancer cells. The gene discussed is TP53; the disease is breast cancer.