NF-kappa B activates prostate-specific antigen expression and is upregulated in androgen-independent prostate cancer.

The transcription factor NF-kappaB regulates gene expression involved in cell growth and survival and has been implicated in progression of hormone-independent breast cancer. By expressing a dominant-active form of mitogen-activated protein kinase kinase kinase 1, by exposure to tumor necrosis factor alpha, or by overexpression of p50/p65, we show that NF-kappaB activates a transcription regulatory element of the prostate-specific antigen (PSA)-encoding gene, a marker for prostate cancer development, treatment, and progression. By DNase I footprinting, we identified four NF-kappaB binding sites in the PSA core enhancer. We also demonstrate that androgen-independent prostate cancer xenografts have higher constitutive NF-kappaB binding activity than their androgen-dependent counterparts. These results suggest a role of NF-kappaB in prostate cancer progression.