The proto‐oncogene/translation factor eIF4E: A survey of its expression in breast carcinomas

The eukaryotic translation initiation factor elF‐4E binds to the cap structure of mRNAs as one component of the elF‐4 translation initiation complex, which mediates the recruitment of mRNA to the ribosomes. Overexpression of elF‐4E can result in oncogenic transformation and uncontrolled growth of mammalian cells, presumably by facilitating the expression of growth‐control gene products which are normally translationally repressed. Whereas the mechanism of elF‐4E‐mediated transformation is being actively pursued, clinical investigations into the expression of elF‐4E in prevalent human cancers are lacking. We have recently initiated a screen of breast carcinomas by probing with elF‐4E antiserum. Using Western blots, we have analyzed the level of elF‐4E in 38 carcinomas, 7 normal samples and 3 fibroadenomas. We found that elF‐4E was elevated 3‐ to 10‐fold in virtually all the carcinomas we analyzed, but not in fibroadenomas. This analysis was also confirmed by immunohistological staining in situ, showing that overexpression of elF‐4E can be readily identified at the single‐cell level. Our results suggest that an elevation of elF‐4E may be an essential component in the development of breast cancer. © 1995 Wiley‐Liss, Inc.

[1]  N. Sonenberg Translation factors as effectors of cell growth and tumorigenesis. , 1993, Current opinion in cell biology.

[2]  A. De Benedetti,et al.  Decreasing the level of translation initiation factor 4E with antisense rna causes reversal of ras‐mediated transformation and tumorigenesis of cloned rat embryo fibroblasts , 1993, International journal of cancer.

[3]  R. Rhoads Regulation of eukaryotic protein synthesis by initiation factors. , 1993, The Journal of biological chemistry.

[4]  N. Sonenberg,et al.  mRNAs containing extensive secondary structure in their 5′ non‐coding region translate efficiently in cells overexpressing initiation factor eIF‐4E. , 1992, The EMBO journal.

[5]  N. Sonenberg,et al.  A fraction of the mRNA 5' cap-binding protein, eukaryotic initiation factor 4E, localizes to the nucleus. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[6]  R. Rhoads Protein synthesis, cell growth and oncogenesis. , 1991, Current opinion in cell biology.

[7]  M. Kozak,et al.  An analysis of vertebrate mRNA sequences: intimations of translational control , 1991, The Journal of cell biology.

[8]  A. De Benedetti,et al.  Expression of antisense RNA against initiation factor eIF-4E mRNA in HeLa cells results in lengthened cell division times, diminished translation rates, and reduced levels of both eIF-4E and the p220 component of eIF-4F , 1991, Molecular and cellular biology.

[9]  A. De Benedetti,et al.  Overexpression of eukaryotic protein synthesis initiation factor 4E in HeLa cells results in aberrant growth and morphology. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[10]  N. Sonenberg,et al.  Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' cap , 1990, Nature.

[11]  R. Love Antiestrogens as chemopreventive agents in breast cancer: promise and issues in evaluation. , 1989, Preventive medicine.

[12]  R. Rhoads,et al.  Cap recognition and the entry of mRNA into the protein synthesis initiation cycle. , 1988, Trends in biochemical sciences.

[13]  M. Kozak An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. , 1987, Nucleic acids research.

[14]  N. Sonenberg,et al.  The involvement of mRNA secondary structure in protein synthesis. , 1987, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[15]  J. Hershey,et al.  Regulated phosphorylation and low abundance of HeLa cell initiation factor eIF-4F suggest a role in translational control. Heat shock effects on eIF-4F. , 1987, The Journal of biological chemistry.

[16]  Harvey F. Lodish,et al.  Model for the regulation of mRNA translation applied to haemoglobin synthesis , 1974, Nature.