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Eukaryotic Initiation Factors (eIF) 2 and 4E Expression, Localization, and Phosphorylation in Brain Tumors

Sonia Tejada, M. Val T. Lobo, Mercedes García-Villanueva, Silvia Sacristán, M. Isabel Pérez-Morgado, Matilde Salinas and M. Elena Martín

Servicio de Neurocirugía (ST), Servicio de Anatomía Patológica (MG-V), Servicio de Neurobiología-Investigación (SS), and Servicio de Bioquímica-Investigación (MIP-M,MS,MEM), Hospital Ramón y Cajal, Madrid, Spain, and Departamento de Biología Celular y Genética, Universidad de Alcalá, Madrid, Spain (MVTL)

Correspondence to: M. Elena Martín, Servicio de Bioquímica, Departamento de Investigación, Hospital Ramón y Cajal, Ctra. Colmenar Km. 9, 28034 Madrid, Spain. E-mail: m.elena.martin{at}hrc.es

Increased protein synthesis is regulated, in part, by two eukaryotic translation initiation factors (eIFs): eIF4E and eIF2. One or both of these factors are often overexpressed in several types of cancer cells; however, no data are available at present regarding eIF4E and eIF2 levels in brain tumors. In this study, we analyzed the expression, subcellular localization and phosphorylation states of eIF4E and eIF2 in 64 brain tumors (26 meningiomas, 16 oligodendroglial tumors, and 22 astrocytomas) and investigated the correlation with the expression of MIB-1, p53, and cyclin D1 proteins as well. There are significant differences in the phosphorylated eIF4E levels between the tumors studied, being the highest in meningiomas and the lowest in the oligodendroglial tumors. Relative to subcellular localization, eIF4E is frequently found in the nucleus of the oligodendroglial tumors and rarely in the same compartment of the meningiomas, whereas eIF2 showed an inverse pattern. Finally, cyclin D1 levels directly correlate with the phosphorylation status of both factors. The different expression, phosphorylation, or/and subcellular distribution of eIF2 and eIF4E within the brain types of tumors studied could indicate that different pathways are activated for promoting cell cycle proliferation, for instance, leading to increased cyclin D1 expression. (J Histochem Cytochem 57:503–512, 2009)

Key Words: eukaryotic translation initiation factor 2 • eukaryotic translation initiation factor 4E • cyclin D1 • brain tumors • translation

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