Upregulation of protein synthesis initiation factor eIF-4E is an early event during colon carcinogenesis

Igor B. Rosenwald, Jane Jane Chen, Songtao Wang, Lou Savas, Irving M. London, James M. Pullman

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

A general increase in protein synthesis and a specific increase in the synthesis of growth-promoting proteins are necessary for mitogenesis. Regulation of protein synthesis, as well as preferential translation of some mRNAs coding for growth promoting proteins (e.g. cyclin D1), involves the essential protein synthesis initiation factor eIF-4E. This factor is induced by various oncoproteins, and, when overexpressed, it can transform cultured cells. In this report we explore the roles of eIF-4E in human neoplastic disorders of the colon and in the regulation of general and specific protein synthesis. We find that elF-4E is increased in colon adenomas and carcinomas, and this increase is accompanied in most but not all cases by elevation of cyclin D1 levels. While general protein synthesis is increased by eIF-4E overexpression in cultured cells, only a small proportion of proteins is preferentially upregulated by eIF-4E, as revealed by two-dimensional gel electrophoresis. These results are consistent with the view that eIF-4E plays a role in carcinogenesis by increasing general protein synthesis and by preferentially upregulating a subset of putative growth promoting proteins. Our results, taken together with the recent findings that c-myc transcription is negatively regulated by APC and our earlier data on transcriptional activation of eIF-4E expression by c-Myc suggest that eIF-4E is a downstream target of the APC/β-catenin/Tcf-4 pathway, and is strongly involved in colon tumorigenesis.

Original languageEnglish (US)
Pages (from-to)2507-2517
Number of pages11
JournalOncogene
Volume18
Issue number15
DOIs
StatePublished - Apr 15 1999
Externally publishedYes

Fingerprint

Peptide Initiation Factors
Colon
Carcinogenesis
Up-Regulation
Proteins
Cyclin D1
Cultured Cells
Growth
Catenins
Oncogene Proteins
Electrophoresis, Gel, Two-Dimensional
Protein Biosynthesis
Adenoma
Transcriptional Activation
Carcinoma

Keywords

  • Colon cancer
  • Cyclins
  • eIF-4E
  • Protein synthesis
  • Transformation
  • Translation factors

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Upregulation of protein synthesis initiation factor eIF-4E is an early event during colon carcinogenesis. / Rosenwald, Igor B.; Chen, Jane Jane; Wang, Songtao; Savas, Lou; London, Irving M.; Pullman, James M.

In: Oncogene, Vol. 18, No. 15, 15.04.1999, p. 2507-2517.

Research output: Contribution to journalArticle

Rosenwald, Igor B. ; Chen, Jane Jane ; Wang, Songtao ; Savas, Lou ; London, Irving M. ; Pullman, James M. / Upregulation of protein synthesis initiation factor eIF-4E is an early event during colon carcinogenesis. In: Oncogene. 1999 ; Vol. 18, No. 15. pp. 2507-2517.
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