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

Background. When resting cells are stimulated by growth factors, an increas e in protein synthesis follows that depends in part on two key eukaryotic t ranslation initiation factors, 4E and 2 alpha (eIF-4E and eIF-2 alpha, resp ectively). In the normal cell, expression and activity of both factors are increased transiently, whereas they become elevated constitutively in oncog ene-transformed cultured cells, and overexpression of either initiation fac tor in rodent cells makes them tumorigenic. In this study, the authors inve stigated an association between the expression of these translation initiat ion factors and lung carcinogenesis. Methods. The authors analyzed the expression of the protein synthesis initi ation factors eIF-4E and eIF-2 alpha by immunohistochemistry in bronchioloa lveolar (BA) and squamous cell (SC) carcinomas of the lung. Western blot an alysis was performed to validate the specificity of antibodies in detecting their cognate proteins. Results. Both eIF-4E and eIF-2 alpha were increased frequently in BA carcin omas, 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-2 alpha. Conclusions. Increased expression of either one or both translation initiat ion factors may facilitate accelerated grow-th and division of neoplastic c ells in BA carcinoma of the lung. However, the current findings suggest a p ossibility that increased cell growth and proliferation in SC carcinoma may be achieved through a mechanism independent of increases in eIF-4E and eIF -2 alpha expression. Cancer 2001;92:2164-71. (C) 2001 American Cancer Socie ty.