more evidence of the central role of NF-kappaB in panc cancer

Discussion in 'Health and medical' started by Roger, Feb 16, 2004.

  1. Roger

    Roger Guest

    Oncogene. 1999 Aug 12;18(32):4554-63.

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

    Wang W, Abbruzzese JL, Evans DB, Chiao PJ. Department of Surgical Oncology, The University of Texas
    MD Andersen Cancer Center, Houston, Texas, TX 77030, USA.

    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.