Title

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

UMMS Affiliation

Department of Pathology

Publication Date

5-6-1999

Document Type

Article

Subjects

3T3 Cells; Adenocarcinoma; Adenoma; Animals; Blotting, Western; Cell Transformation, Neoplastic; Colonic Neoplasms; Cyclin D1; Eukaryotic Initiation Factor-4E; Humans; Immunohistochemistry; Mice; Peptide Initiation Factors; Protein Biosynthesis; Tumor Cells, Cultured; Up-Regulation

Disciplines

Life Sciences | Medicine and Health Sciences

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 eIF-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/beta-catenin/Tcf-4 pathway, and is strongly involved in colon tumorigenesis.

Rights and Permissions

Citation: Oncogene. 1999 Apr 15;18(15):2507-17. Link to article on publisher's site

DOI of Published Version

10.1038/sj.onc.1202563

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Oncogene

PubMed ID

10229202