Eukaryotic Initiation Factors (EIF) 2 and 4e Expression, Localization, and Phosphorylation in Brain Tumors

Sonia Tejada ¹, M. Val T. Lobo ¹, Mercedes García-Villanueva ¹, Silvia Sacristán ¹, M. Isabel Pérez-Morgado ¹, Matilde Salinas ¹ and M. Elena Martín ^1*

¹ Servicio de Neurocirugía (ST), Servicio de Anatomía Patológica (MG-V), Servicio de Neurobiología-Investigación (SS), 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)

^* To whom correspondence should be addressed. E-mail: m.elena.martin{at}hrc.es.

Submitted on September 29, 2008
Accepted on 15 January 2009

	Abstract

The 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 sixty-four brain tumors (26 meningiomas, 16 oligodendrioglial 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 oligodendrioglial tumors. Relative to the subcellular localization, eIF4E is frequently found in the nucleus of the oligodendrioglial tumors and rarely in the same compartment of the meningiomas while eIF2 showed the inverse pattern. Finally, cyclin D1 levels directly correlate with the phosphorylation status of both factors. The different expression, phosphorylation or/and subcelular 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.

Key Words: eIF2, eIF4E, cyclin D1, brain tumors, translation

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