NF-kappa B activates prostate-specific antigen expression and is upregulated in androgen-independent prostate cancer.
The transcription factor NF-kappa B 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-kappa B 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-kappa B binding sites in the PSA core enhancer. We also demonstrate that androgen-independent prostate cancer xenografts have higher constitutive NF-kappa B binding activity than their androgen-dependent counterparts. These results suggest a role of NF-kappa B in prostate cancer progression.
Chen
Charlie D
CD
Division of Hematology/Oncology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1678, USA.
Sawyers
Charles L
CL
D000728:Androgens / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000728:Androgens; D016328:NF-kappa B; D017430:Prostate-Specific Antigen; D013755:Tetradecanoylphorbol Acetate