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). The gene discussed is ESR1; the disease is breast cancer.