title: Increased levels of the translation initiation factor eIF4E in differentiating epithelial lung tumor cell lines.
abstract: Rates of eukaryotic protein synthesis and proliferation are dependent upon the availability of eIF4F, the cap-binding translation initiation complex that guides the ribosome onto the mRNA. One possible rate-limiting factor in eIF4F complex formation is the availability of eIF4E, which interacts specifically with the mRNA cap structure. As such, it has a potential role in the selective translation of growth-related mRNAs, with overexpression of eIF4E resulting in aberrant cell growth and transformation. A number of studies suggest that eIF4E may play a role in cellular differentiation as well as proliferation. We have previously reported that post-transcriptional regulation is involved in the induction of keratins in epithelial lung tumor cell lines exposed to the differentiation-modulating agent, bromo-deoxyuridine (BrdU). Here, we demonstrate that these BrdU-treated lung cells express elevated levels of eIF4E protein and enhanced phosphorylation of eIF4E. Overexpression of eIF4E by cDNA transfection in the poorly differentiated, keratin-negative human lung cell line, DLKP, was found to promote a flattened, more epithelial appearance to these cells, coupled with the induction of simple keratins (keratins 8 and 18). In contrast, levels of eIF4E expression were found to decrease during BrdU-induced differentiation of the leukemic cell line, HL-60, suggesting that there are cell-type differences in the response to BrdU and in the requirement for eIF4E during differentiation.
authors.affiliation: National Cell and Tissue Culture Centre/National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Ireland.
authors.forename: Derek
authors.initials: D
authors.lastname: Walsh
authors.forename: Paula
authors.initials: P
authors.lastname: Meleady
authors.forename: Brendan
authors.initials: B
authors.lastname: Power
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Morley
authors.forename: Martin
authors.initials: M
authors.lastname: Clynes
mesh_terms: D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D004848:Epithelium / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D006801:Humans; D053533:Keratin-8; D007633:Keratins / Q000096:biosynthesis / Q000235:genetics; D008175:Lung Neoplasms / Q000378:metabolism*
chemical_list: D039561:Eukaryotic Initiation Factor-4E; C426203:KRT8 protein, human; D053533:Keratin-8; D007633:Keratins; D001973:Bromodeoxyuridine