Morphoproteomic confirmation of constitutively activated mTOR, ERK, and NF-kappaB pathways in Ewing family of tumors

Maryam J Zenali; Ping L Zhang; Anne E Bendel; Robert E Brown

Morphoproteomic confirmation of constitutively activated mTOR, ERK, and NF-kappaB pathways in Ewing family of tumors

Ann Clin Lab Sci. 2009 Spring;39(2):160-6.

Authors

Maryam J Zenali¹, Ping L Zhang, Anne E Bendel, Robert E Brown

Affiliation

¹ 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.

PMID: 19429803

Abstract

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.

MeSH terms

12E7 Antigen
Antigens, CD / physiology
Cell Adhesion Molecules / physiology
Cell Line, Tumor
Cell Nucleus / metabolism
Cell Nucleus / pathology
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
Extracellular Signal-Regulated MAP Kinases / genetics
Extracellular Signal-Regulated MAP Kinases / metabolism*
Flavonoids / pharmacology
Gene Expression Profiling
Humans
NF-kappa B / genetics
NF-kappa B / metabolism*
Neuroectodermal Tumors / genetics
Neuroectodermal Tumors / metabolism*
Phosphorylation
Protein Kinases / genetics
Protein Kinases / metabolism*
Proteome
RNA, Messenger / genetics
Sarcoma, Ewing / enzymology
Sarcoma, Ewing / metabolism*
Signal Transduction / physiology
TOR Serine-Threonine Kinases
Transforming Growth Factor beta / genetics
Up-Regulation / drug effects

Substances

12E7 Antigen
Antigens, CD
CD99 protein, human
Cell Adhesion Molecules
Flavonoids
NF-kappa B
Proteome
RNA, Messenger
Transforming Growth Factor beta
Protein Kinases
MTOR protein, human
TOR Serine-Threonine Kinases
Extracellular Signal-Regulated MAP Kinases
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one