In the current study, we revealed a transcriptional mechanism by which NF-κB recruits a histone acetyltransferase p300 and the estrogen-activated NCOA3 to induce the expression of BCL2, BCL2A1, BCL2L2, and MCL1, but not BCL2L1. Knockdown or pharmacological inhibition of NCOA3 significantly suppressed the expression of BCL2, BCL2A1, BCL2L2, and MCL1, suggesting that targeting NCOA3 or disrupting the NCOA3-p300-NF-κB complex may represent new therapeutic strategies for treating breast cancer. The gene discussed is MCL1; the disease is breast carcinoma.