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Overexpression of urokinase-type plasminogen activator in pancreatic adenocarcinoma is regulated by constitutively activated RelA.

Publication ,  Journal Article
Wang, W; Abbruzzese, JL; Evans, DB; Chiao, PJ
Published in: Oncogene
August 12, 1999

The Rel/NF-kappaB transcription factors regulate the expression of many genes. The activity of RelA, a member of the Rel/NF-kappaB transcription factor family, is constitutively activated in the majority of pancreatic adenocarcinomas and cell lines. We report that the urokinase-type plasminogen activator (uPA), one of the critical proteases involved in tumor invasion and metastasis, is overexpressed in pancreatic tumor cells and its overexpression is induced by constitutive RelA activity. The uPA promoter contains an NF-kappaB binding site that directly mediates the induction of uPA expression by RelA. Expression of a dominant-negative IkappaBalpha mutant inhibits kappaB site-dependent transcriptional activation of a uPA promoter-CAT reporter gene. Treating the pancreatic tumor cell lines with the known NF-kappaB inhibitors, dexamethasone and n-tosylphenyalanine chloromethyl ketone (TPCK), abolishes constitutive RelA activity and uPA overexpression. These results show that uPA is one of the downstream target genes induced by constitutively activated RelA in human pancreatic tumor cells, and suggests that constitutive RelA activity may play a critical role in tumor invasion and metastasis. Inhibition of constitutive RelA in pancreatic tumor cells may reduce their invasive and metastatic potential.

Duke Scholars

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

August 12, 1999

Volume

18

Issue

32

Start / End Page

4554 / 4563

Location

England

Related Subject Headings

  • Urokinase-Type Plasminogen Activator
  • Tumor Cells, Cultured
  • Transcription, Genetic
  • Transcription Factor RelA
  • Tosylphenylalanyl Chloromethyl Ketone
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • NF-kappa B
  • Humans
  • Gene Expression Regulation, Neoplastic
 

Citation

APA
Chicago
ICMJE
MLA
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Wang, W., Abbruzzese, J. L., Evans, D. B., & Chiao, P. J. (1999). Overexpression of urokinase-type plasminogen activator in pancreatic adenocarcinoma is regulated by constitutively activated RelA. Oncogene, 18(32), 4554–4563. https://doi.org/10.1038/sj.onc.1202833
Wang, W., J. L. Abbruzzese, D. B. Evans, and P. J. Chiao. “Overexpression of urokinase-type plasminogen activator in pancreatic adenocarcinoma is regulated by constitutively activated RelA.Oncogene 18, no. 32 (August 12, 1999): 4554–63. https://doi.org/10.1038/sj.onc.1202833.
Wang, W., et al. “Overexpression of urokinase-type plasminogen activator in pancreatic adenocarcinoma is regulated by constitutively activated RelA.Oncogene, vol. 18, no. 32, Aug. 1999, pp. 4554–63. Pubmed, doi:10.1038/sj.onc.1202833.

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

August 12, 1999

Volume

18

Issue

32

Start / End Page

4554 / 4563

Location

England

Related Subject Headings

  • Urokinase-Type Plasminogen Activator
  • Tumor Cells, Cultured
  • Transcription, Genetic
  • Transcription Factor RelA
  • Tosylphenylalanyl Chloromethyl Ketone
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • NF-kappa B
  • Humans
  • Gene Expression Regulation, Neoplastic