Increased levels of the translation initiation factor eIF4E in differentiating epithelial lung tumor cell lines

Derek Walsh, Paula Meleady*, Brendan Power, Simon J. Morley, Martin Clynes

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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, bromodeoxyuridine (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.

Original languageEnglish (US)
Pages (from-to)126-134
Number of pages9
JournalDifferentiation
Volume71
Issue number2
DOIs
StatePublished - Jan 1 2003

Keywords

  • 5-bromodeoxyuridine
  • Epithelial cell differentiation
  • Eukaryotic initiation factor 4E
  • Keratins 8 and 18

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology
  • Cancer Research

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