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

Abstract

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-κB) signaling pathway, which regulates cell proliferation, inflammation, migration and apoptosis. The prolyl isomerase, Pin1, has been found to bind directly to the NF-κB protein, p65, and cause increases in NF-κB 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-κB 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-κB regulated genes due to Pin1 knockdown. Taken together, these data suggest that Pin1 is an important regulator of NF-κB in GBM, and support the notion of using Pin1 as a therapeutic target in the future.

DOI: 10.1038/onc.2009.232

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Cite this paper

@article{Atkinson2009ThePI, title={The prolyl isomerase Pin1 regulates the NF-κB signaling pathway and interleukin-8 expression in glioblastoma}, author={George P Atkinson and Susan E. Nozell and Dion K. Harrison and Mark S Stonecypher and D Chen and Etty Nadia Benveniste}, journal={Oncogene}, year={2009}, volume={28}, pages={3735-3745} }