Morphoproteomic confirmation of constitutively activated mTOR, ERK, and NF-kappaB pathways in high risk neuro-blastoma, with cell cycle and protein analyte correlates.
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.
Brown
Robert E
RE
Department of Pathology and Laboratory Medicine, University of Texas Medical School-Houston Medical School, Houston, TX 77030, USA. robert.brown@uth.tmc.edu
Tan
Dongfeng
D
Taylor
Jeffrey S
JS
Miller
Michal
M
Prichard
Jeffrey W
JW
Kott
Marylee M
MM
D000951:Antigens, Neoplasm / Q000032:analysis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D052002:NF-kappa B p50 Subunit / Q000032:analysis / Q000378:metabolism*; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D011494:Protein Kinases / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D044786:S-Phase Kinase-Associated Proteins; D011494:Protein Kinases; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases