TP53 and breast cancer: In addition, MDM2 promoter activity is increased through the p53-binding site in the MDM2 gene in cells expressing the thyroid hormone receptor (Qi et al., 1999) and through multiple transcription-factor response elements in estrogen receptor (ER) α-positive breast cancer cells (Phelps et al., 2003), and p16INK4a reporter activity is increased in senescent cells in comparison with that in young cells (Wang et al., 2001).