Signal transduction-mediated regulation of urokinase gene expression in human prostate cancer

Jonathan A. Eandi, Joy C. Yang, Christopher P Evans

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Urokinase-type plasminogen activator (u-PA) contributes to tumor progression in prostate cancer (CAP). We have previously shown that u-PA expression is upregulated through the AP-1 and PEA3 sites and repressed by androgen. However, signaling pathways mediating u-PA gene expression in CaP are not delineated. We hypothesized that MAPK pathways mediate u-PA in CaP, and thereby studied specific ERK, JNK, and P38-MArK pathway mutant constructs and inhibitors in vitro. Human, androgen insensitive CaP PC3 cells stably transfected with the androgen receptor expression vector and vector alone were used. A u-PA promoter CAT vector transiently expressed with dominant negative mutant signaling constructs was studied. All mutants drastically reduced u-PA promoter activity. Furthermore, inhibition of PI3K, an upstream regulator in the JNK/SAPK pathway, decreased u-PA promoter transcription. Collectively, these results show that MArK pathways ERK, JNK/SAPK, and P38-MArK represent a significant component in the regulation of u-PA expression in human CaP.

Original languageEnglish (US)
Pages (from-to)521-527
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume288
Issue number3
DOIs
StatePublished - Nov 2 2001

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Signal transduction
Urokinase-Type Plasminogen Activator
Gene Expression Regulation
Gene expression
Signal Transduction
Prostatic Neoplasms
MAP Kinase Signaling System
Androgens
Transcription Factor AP-1
Androgen Receptors
p38 Mitogen-Activated Protein Kinases
Transcription
Phosphatidylinositol 3-Kinases
Tumors
Gene Expression

Keywords

  • MARK
  • Prostate cancer
  • Signal transduction
  • Urokinase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Signal transduction-mediated regulation of urokinase gene expression in human prostate cancer. / Eandi, Jonathan A.; Yang, Joy C.; Evans, Christopher P.

In: Biochemical and Biophysical Research Communications, Vol. 288, No. 3, 02.11.2001, p. 521-527.

Research output: Contribution to journalArticle

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