Elevated expression of eIF4E in confined early breast cancer lesions: possible role of hypoxia.

Abstract:

:The translation-initiation factor eIF4E is rate-limiting for protein synthesis, and its over-expression results in oncogenic transformation of mammalian cells. eIF4E facilitates the synthesis of several powerful tumor angiogenic factors (FGF-2 and VEGF) by selectively enhancing their translation. In breast carcinomas, eIF4E is commonly over-expressed, but the pathology where this elevation is initially manifested is presently unknown. To probe whether the elevation of eIF4E marks an early stage of cancer development, we focused our research on early cancerous lesions. We have analyzed 70 invasive ductal carcinomas (IDCs), 78 ductal carcinomas in situ (DCIS), 51 benign lesions and 4 model cell lines for elevated expression of eIF4E by several different methods: Northern/Western blots, immuno-histochemistry and in situ RT-PCR. eIF4E expression was markedly increased in IDC and in islets of viable cells in the center of poorly vascularized DCIS, which are not easily identifiable by standard histological stains. We also show that expression of eIF4E is increased by hypoxia and, presumably, in hypoxic areas of these lesions. We propose that clonal expansion of cancer cells, permanently over-expressing eIF4E, gives them a critical advantage to survive hypoxia and marks the transition toward the vascular phase of cancer progression. Hence, eIF4E may be useful in stratifying DCIS lesions according to their malignant stage.

journal_name

Int J Cancer

authors

DeFatta RJ,Turbat-Herrera EA,Li BD,Anderson W,De Benedetti A

doi

10.1002/(sici)1097-0215(19990209)80:4<516::aid-ijc

subject

Has Abstract

pub_date

1999-02-09 00:00:00

pages

516-22

issue

4

eissn

0020-7136

issn

1097-0215

pii

10.1002/(SICI)1097-0215(19990209)80:4<516::AID-IJC

journal_volume

80

pub_type

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