Transcriptional activation of the human prostatic acid phosphatase gene by NF-κB via a novel hexanucleotide-binding site

Stanislav Zelivianski, Richard Glowacki, Ming-Fong Lin

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 κB (NF-κB)-binding site that is required for NF-κB up-regulation in prostate cancer cells, while NF-κB failed to have the same effect in HeLa cells. Conversely, inhibition of the NF-κB pathway stopped p65 NF-κB activation of the p1356 promoter activity. Gel shift and mutation analyses determined that AGGTGT (-1254/-1249) is the core sequence for NF-κB-binding and activation. Biologically, tumor necrosis factor-α (TNF-α) activated endogenous PAcP expression in LNCaP human prostate cancer cells. The data collectively indicate that NF-κB 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.

Original languageEnglish (US)
Pages (from-to)3566-3580
Number of pages15
JournalNucleic acids research
Volume32
Issue number12
DOIs
StatePublished - Sep 13 2004

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Transcriptional Activation
Binding Sites
Prostatic Neoplasms
Genes
Up-Regulation
Protein Tyrosine Phosphatases
Differentiation Antigens
Electrophoretic Mobility Shift Assay
Prostate-Specific Antigen
prostatic acid phosphatase
HeLa Cells
Cervix Uteri
Androgens
Sequence Analysis
Epithelium
Tumor Necrosis Factor-alpha
Cell Proliferation
Carcinoma
Mutation

ASJC Scopus subject areas

  • Genetics

Cite this

Transcriptional activation of the human prostatic acid phosphatase gene by NF-κB via a novel hexanucleotide-binding site. / Zelivianski, Stanislav; Glowacki, Richard; Lin, Ming-Fong.

In: Nucleic acids research, Vol. 32, No. 12, 13.09.2004, p. 3566-3580.

Research output: Contribution to journalArticle

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