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Morphoproteomic Confirmation of Constitutively Activated mTOR, ERK, and NF-kappaB Pathways in High Risk Neuro-blastoma, with Cell Cycle and Protein Analyte Correlates

Address correspondence to Robert E. Brown, M.D., Department of Pathology & Laboratory Medicine, University of Texas Medical School-Houston, 6431 Fannin Street, MSB 2.286, Houston, TX 77030, USA; tel 713 500 5332; fax 713 500 0695; e-mail robert.brown{at}uth.tmc.edu.

Morphoproteomic analysis reveals the constitutive activation of the mTOR, ERK, and NF-kappaB pathways in high risk neuroblastoma (HRN) cases as evidenced by (a) collective commonalities of: phosphorylated (p)-mTOR, p70S6K, ERK 1/2, and NF-kappaBp65 protein analytes using phosphospecific probes directed against sites of activation; (b) nuclear translocation of p-p70S6K, p-ERK 1/2, and p-NF-kappaBp65; and (c) correlative expression of the S phase-associated kinase Skp-2 (at a relatively high percentage in tumoral nuclei) and of the anti-apoptotic protein bcl-2. Based on a review of the literature, these preliminary observations appear to be the first morphoproteomic study on primary neuroblastomas.

Keywords: neuroblastoma, mTOR, ERK, NF-kappaB, cell cycle, morphoproteomics