BCAS2 was identified through differential display analysis as an mRNA species that was overexpressed in MCF7 and BT-20 breast cancer cell lines. The chromosomal region containing this gene, 1p13.3021, is amplified in these cells lines. BCAS2 is a transcriptional cofactor that enhances estrogen receptor-mediated gene expression, and directly interacts with the tumor suppressor p53 to reduce p53 transcriptional activity by reducing p53 protein level in the absence of DNA damage. Deprivation of BCAS2 through RNA inhibition induces apoptosis in p53-wild type cells, but causes G2-M arrest in p53-null or –mutant cells; this effect was reversed with the expression of ectopic BCAS2. BCAS2 may thus be potentially useful as a therapeutic target in the treatment of cancer.