Published online 7 July 2004
Nucleic Acids Research, Vol. 32 No. 12 © Oxford University Press 2004; all rights reserved
Transcriptional activation of the human prostatic acid phosphatase gene by NF-
B via a novel hexanucleotide-binding site
1 Department of Biochemistry and Molecular Biology and 2 Department of Surgery/Urology, College of Medicine and 3 Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha NE 68198, USA
* To whom correspondence should be addressed at Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha NE 68198, USA. Tel: +1 402 559 6658; Fax: +1 402 559 6650; Email: mlin{at}unmc.edu
Current address: Stanislav Zelivianski, Children's Memorial Institute for Education and Research, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, 2430 N Halsted Street, MB218, Chicago, IL 60614, USA
Received as resubmission May 10, 2004; Accepted June 9, 2004
Human prostatic acid phosphatase (PAcP) is a prostate epithelium-specific differentiation antigen. Cellular PAcP functions as a neutral protein tyrosine phosphatase and is involved in regulating androgen-promoted prostate cancer cell proliferation. Despite the fact that the promoter of the PAcP gene has been cloned, the transcriptional factors that regulate PAcP expression remain unidentified. This article describes our analyses of the promoter of the PAcP gene. Deletion analyses of the promoter sequence up to –4893 (–4893/+87) revealed that a 577 bp fragment (–1356/–779) represents the unique positive cis-active element in human prostate cancer cells but not in HeLa cervix carcinoma cells. Interestingly, the 577 bp fragment contains a non-consensus nuclear factor 
B (NF-B)-binding site that is required for NF-B up-regulation in prostate cancer cells, while NF-B failed to have the same effect in HeLa cells. Conversely, inhibition of the NF-B pathway stopped p65 NF-B activation of the p1356 promoter activity. Gel shift and mutation analyses determined that AGGTGT (–1254/–1249) is the core sequence for NF-B-binding and activation. Biologically, tumor necrosis factor-
(TNF-) activated endogenous PAcP expression in LNCaP human prostate cancer cells. The data collectively indicate that NF-B up-regulates PAcP promoter activity via its binding to the AGGTGT motif, a novel binding sequence located inside the cis-active enhancer element in human prostate cancer cells.
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