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 journalArticlepeer-review

11 Scopus citations


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
Issue number3
StatePublished - Nov 2 2001


  • MARK
  • Prostate cancer
  • Signal transduction
  • Urokinase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology


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