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Molecular and Cellular Biology, April 2002, p. 2862-2870, Vol. 22, No. 8
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.8.2862-2870.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

NF-{kappa}B Activates Prostate-Specific Antigen Expression and Is Upregulated in Androgen-Independent Prostate Cancer

Charlie D. Chen and Charles L. Sawyers*

Division of Hematology/Oncology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1678

Received 12 December 2001/ Accepted 19 January 2002

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.

* Correspondent author. Mailing address: 11-934 Factor Building, UCLA-Hematology-Oncology, 10833 Le Conte Ave., Los Angeles, CA 90095-1678. Phone: (310) 206-5585. Fax: (310) 206-8502. E-mail: csawyers{at}mednet.ucla.edu.

Molecular and Cellular Biology, April 2002, p. 2862-2870, Vol. 22, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.8.2862-2870.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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