The prolyl isomerase Pin1 regulates the NF-B signaling pathway and interleukin-8 expression in glioblastoma

Academic Article


  • The brain tumor glioblastoma (GBM) remains one of the most aggressive and devastating tumors despite decades of effort to find more effective treatments. A hallmark of GBM is the constitutive activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) signaling pathway, which regulates cell proliferation, inflammation, migration and apoptosis. The prolyl isomerase, Pin1, has been found to bind directly to the NF-B protein, p65, and cause increases in NF-B promoter activity in a breast cancer model. We now present evidence that this interaction occurs in GBM and that it has important consequences on NF-B signaling. We demonstrate that Pin1 levels are enhanced in primary GBM tissues compared with controls, and that this difference in Pin1 expression affects the migratory capacity of GBM-derived cells. Pin1 knockdown decreases the amount of activated, phosphorylated p65 in the nucleus, resulting in inhibition of the transcriptional program of the IL-8 gene. Through the use of microarray, we also observed changes in the expression levels of other NF-B regulated genes due to Pin1 knockdown. Taken together, these data suggest that Pin1 is an important regulator of NF-B in GBM, and support the notion of using Pin1 as a therapeutic target in the future. © 2009 Macmillan Publishers Limited All rights reserved.
  • Published In

  • Oncogene  Journal
  • Digital Object Identifier (doi)

    Author List

  • Atkinson GP; Nozell SE; Harrison DK; Stonecypher MS; Chen D; Benveniste EN
  • Start Page

  • 3735
  • End Page

  • 3745
  • Volume

  • 28
  • Issue

  • 42