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Annals of Clinical & Laboratory Science 36:421-426 (2006)
© 2006 Association of Clinical Scientists

Communication

Morphoproteomic Demonstration of Constitutive Nuclear Factor-kappaB Activation in Glioblastoma Multiforme with Genomic Correlates and Therapeutic Implications

Robert E. Brown1 and Amy Law2
1 Division of Laboratory Medicine and 2 Department of Adult Hematology and Oncology, Geisinger Medical Center, Danville, Pennsylvania

Address correspondence to Robert E. Brown, M.D., at his new address: Department of Pathology, University of Texas Medical School, 6431 Fannin Street, MSB 2.286, Houston, TX 77030, USA; tel 713 500 5332; fax 713 500 0733; e-mail robert.brown{at}uth.tmc.edu.

Glioblastoma multiforme (GBM) presents a major challenge to neurosurgeons, neuro-oncologists, and radiation therapists by virtue of its location with a blood-brain barrier, chemoradioresistance, highly malignant phenotype, and angiogenic potential. Because nuclear factor-kappaB (NF-{kappa}B) can transcriptionally activate genes leading to the synthesis of anti-apoptotic, chemoresistant, growth promoting, and angiogenic proteins; we assessed the state of activation of NF-{kappa}B in 6 GBM cases at diagnosis. Morphoproteomic analysis confirmed the constitutive activation of NF-{kappa}B by demonstrating the phosphorylation (p) and nuclear translocation of p-NF-{kappa}Bp65 (Ser 536) in these cases. This observation coincides with (a) previous immunohistochemical findings showing nuclear translocation of total p65, (b) demonstration of NF-{kappa}B DNA binding activity, (c) the results of electrophoretic mobility shift assays, and (d) existing genomic data in GBM. Furthermore, such constitutive activation of the NF-{kappa}B pathway helps to explain some of the tumor biology and supports the incorporation of NF-{kappa}B pathway inhibitors into the treatment of GBM.

Keywords: glioblastoma multiforme, nuclear factor-kappaB, tumor morphoproteomics






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