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Annals of Clinical & Laboratory Science 39:160-166 (2009)
© 2009 Association of Clinical Scientists

Morphoproteomic Confirmation of Constitutively Activated mTOR, ERK, and NF-kappaB Pathways in Ewing Family of Tumors

Maryam J. Zenali1, Ping L. Zhang2, Anne E. Bendel3 and Robert E. Brown1
1 Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School; 2 Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, Michigan; and 3 Pediatric Hematology/Oncology, Children’s Hospitals and Clinics, Minneapolis, Minnesota

Address correspondence to Robert E. Brown, M.D., 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; tel 713 500 5332; fax 713 500 0695; e-mail robert.brown{at}uth.tmc.edu.

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-kappaBp65; 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.

Keywords: Ewing family of tumors, mTOR, p70S6K, ERK, NF-kappaB, cell cycle, morphoproteomics







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