Morphoproteomic confirmation of constitutively activated mTOR, ERK, and NF-kappaB pathways in Ewing family of tumors.
In 3 patients with the Ewing family of tumors (EFT), morphoproteomic analyses of the tumors revealed constitutive activation of the mTOR, ERK, and NF-kappaB pathways, as evidenced by: (a) expression of phosphorylated (p)-mTOR, p-p70S6K, p-ERK 1/2, and p-NF-kappaB proteins using phosphospecific immunohistochemical probes directed against the activation sites; (b) nuclear translocation of p-p70S6K, p-ERK 1/2, and p-NF-kappaB p65; and (c) correlative expression of Ki-67 and Skp2 proteins consistent with cell cycling consequent to signal transduction by these pathways of convergence. This study examines the cytogenetic and molecular correlates and provides insight into therapeutic strategies relevant to this morphoproteomic profile. Based on a literature review, these observations appear to be the first morphoproteomic study of such pathways of convergence in tumors from EFT patients.
Department of Pathology and Laboratory Medicine, University of Texas Health Science Center-Medical School at Houston, 6431 Fannin Street, MSB 2.286, Houston, TX 77030, USA.
Maryam J
MJ
Zenali
Ping L
PL
Zhang
Anne E
AE
Bendel
Robert E
RE
Brown
D000071443:12E7 Antigen; D015703:Antigens, CD / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D020869:Gene Expression Profiling; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D017599:Neuroectodermal Tumors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D020543:Proteome; D012333:RNA, Messenger / Q000235:genetics; D012512:Sarcoma, Ewing / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D016212:Transforming Growth Factor beta / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D005419:Flavonoids; D016328:NF-kappa B; D020543:Proteome; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one