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

Abstract

The eukaryotic translation initiation factor eIF-4E binds to the cap structure of mRNAs as one component of the eIF-4 translation initiation complex, which mediates the recruitment of mRNA to the ribosomes. Overexpression of eIF-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 eIF-4E-mediated transformation is being actively pursued, clinical investigations into the expression of eIF-4E in prevalent human cancers are lacking. We have recently initiated a screen of breast carcinomas by probing with eIF-4E antiserum. Using Western blots, we have analyzed the level of eIF-4E in 38 carcinomas, 7 normal samples and 3 fibroadenomas. We found that eIF-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 eIF-4E can be readily identified at the single-cell level. Our results suggest that an elevation of eIF-4E may be an essential component in the development of breast cancer.

Elevated expression of eIF4E and FGF-2 isoforms during vascularization of breast carcinomas

“…The level of eIF4E was determined densitometricaly and typically normalized to histone H2B (not shown). All cancer-containing biopsies had 3 ± 30-fold elevated eIF4E, extending our previous analysis (Kereakatte et al, 1995). Notably, the average eIF4E elevation in IDC was 10.5+5.3, in contrast to 2.4+1.1 in DCIS, although we recognize that this analysis is limited to a relatively small number of DCIS samples.…”

“…The polyclonal antiserum to human eIF4E (Kereakatte et al, 1995) was used at 1 : 200 dil. and the factor VIII antiserum (vWF; BioGenex) was used as speci®ed.…”

Decreased proliferation of human melanoma cell lines caused by antisense RNA against translation factor eIF-4A1

“…A relation between translational control and malignant cell transformation became obvious, when elevated levels of eIF-4E as well as reduced levels of the eIF-2a kinase, PKR, were detected in cancer cells (Kerekatte et al, 1995;Nathan et al, 1997;Jagus et al, 1999). Furthermore, overexpression of eIF-4E induced transformation (Rhoads, 1993), and its inhibition by antisense RNA decreased the malignancy of transformed cells (Graff et al, 1995).…”

Detection of the proto-oncogene eIF4E in surgical margins may predict recurrence in head and neck cancer

“…These two potent cytokines can drastically increase vascularization in vivo, which is essential for tumor growth (Folkman et al, 1976). Furthermore, eIF4E was established as a bona ®de tumor marker, as it is uniformly elevated in human breast carcinomas but not in benign ®broadenomas (Kerekatte et al, 1995).…”