In this study, we reveal that Ras up-regulates RbAp46 expression in human breast and bladder cancer cells as well as in mouse fibroblast 7–4 cells, and the binding of RbAp46 with HDAC and Sp1 represses RECK promoter activation via the Sp1 site. The gene discussed is RBBP7; the disease is urinary bladder cancer.