Altered expression of the eukaryotic
translation initiation factor 3 (
eIF3) subunit eIF3e/INT6 has been described in various types of human
cancer, but the nature of its involvement in
tumorigenesis is not yet clear. Using immunohistochemical analysis of 81 primary breast
cancers, we found that high
tumor grade correlated significantly with elevated cytoplasmic eIF3e level in epithelial
tumor cells. Analysis of
protein synthesis after
siRNA-mediated knockdown in
breast cancer cell lines indicated that eIF3e is not required for bulk translation. Microarray analysis of total and polysomal RNAs nonetheless identified distinct sets of mRNAs regulated either positively or negatively by eIF3e; functional classification of these revealed a marked enrichment of genes involved in cell proliferation, invasion and apoptosis. Validated
mRNA targets regulated positively at the translational level by eIF3e included
urokinase-type plasminogen activator and apoptotic regulator BCL-XL, whereas synthesis of
proteins including the mitotic checkpoint component MAD2L1 was negatively regulated. Finally, eIF3e-depleted
breast carcinoma cells showed reduced in vitro invasion and proliferation. Taken together, our study data suggest that eIF3e has a positive role in
breast cancer progression. It regulates the translation, and in some cases abundance, of mRNAs involved in key aspects of
cancer cell biology.