NF-κB Activates Prostate-Specific Antigen Expression and Is Upregulated in Androgen-Independent Prostate Cancer

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Abstract
The transcription factor NF-κB 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-κB 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-κB binding sites in the PSA core enhancer. We also demonstrate that androgen-independent prostate cancer xenografts have higher constitutive NF-κB binding activity than their androgen-dependent counterparts. These results suggest a role of NF-κB in prostate cancer progression.