Expression of eukaryotic translation initiation factors 4E and 2alpha is increased frequently in bronchioloalveolar but not in squamous cell carcinomas of the lung.

Abstract

When resting cells are stimulated by growth factors, an increase in protein synthesis follows that depends in part on two key eukaryotic translation initiation factors, 4E and 2alpha (eIF-4E and eIF-2alpha, respectively). In the normal cell, expression and activity of both factors are increased transiently, whereas they become elevated constitutively in oncogene-transformed cultured cells, and overexpression of either initiation factor in rodent cells makes them tumorigenic. In this study, the authors investigated an association between the expression of these translation initiation factors and lung carcinogenesis. The authors analyzed the expression of the protein synthesis initiation factors eIF-4E and eIF-2alpha by immunohistochemistry in bronchioloalveolar (BA) and squamous cell (SC) carcinomas of the lung. Western blot analysis was performed to validate the specificity of antibodies in detecting their cognate proteins. Both eIF-4E and eIF-2alpha were increased frequently in BA carcinomas, whereas only rarely did SC carcinomas demonstrate elevation of these translation initiation factors. An analysis of cyclin D1 expression did not show a strict correlation with the expression of eIF-4E and eIF-2alpha. Increased expression of either one or both translation initiation factors may facilitate accelerated growth and division of neoplastic cells in BA carcinoma of the lung. However, the current findings suggest a possibility that increased cell growth and proliferation in SC carcinoma may be achieved through a mechanism independent of increases in eIF-4E and eIF-2alpha expression.