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Updated: May 8, 2026

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
Eukaryotic translation initiation factor 4E (eIF4E) expression is associated with breast cancer tumor phenotype and
Tuomas Heikkinen1, Taina Korpela, Rainer Fagerholm
1Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Biomedicum Helsinki, P.O. Box 700, 00029 Helsinki, Finland. tuomas.heikkinen@helsinki.fi
Abstract:
Abnormal translation of mRNAs frequently occurring during carcinogenesis is among the mechanisms that can affect the expression of proteins involved in tumor development and progression. Eukaryotic initiation factor eIF4E is a key regulator of translation of many cancer-related transcripts and its expression is altered in various cancers and has been associated with worse survival. We determined the eIF4E protein levels using immunohistochemistry (IHC) in 1,233 breast tumors on tissue microarrays. We analyzed the effects of the IHC expression level on tumor characteristics and patient survival, also with stratification by adjuvant chemotherapy treatment. In 1,085 successfully stained tumors, high level of eIF4E protein expression was associated with features of aggressive tumor phenotype, namely grade, estrogen and progesterone receptor negativity, HER2 receptor positivity, and high expression of p53 and Ki67, and with triple negative subtype (p < 0.001). High eIF4E expression was associated with worse breast cancer-specific survival with a hazard ratio (HR) of 1.99 (95 % CI 1.32-3.00, p = 0.0008) and was in a multivariate analysis an independent prognostic factor. High eIF4E expression was associated with worse outcome also after detection of distant metastasis (HR = 1.88, 95 % CI 1.20-2.94, p = 0.0060). In the subgroup analysis the survival effect was strongest among patients treated with anthracycline chemotherapy (HR = 3.34, 95 % CI 1.72-6.48, p = 0.0002), whereas no such effect was seen among patients who had not received anthracycline with significant difference in heterogeneity between the two groups (p = 0.0358). High expression of eIF4E is associated with adverse tumor characteristics and predicts poor breast cancer-specific survival. This effect is emphasized in patients treated with anthracycline chemotherapy. eIF4E as a treatment predictive factor warrants further studies.
Insights
High expression of eukaryotic initiation factor eIF4E in breast tumors correlates with aggressive traits and poorer survival. This effect is amplified in patients receiving anthracycline chemotherapy, suggesting eIF4E
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Aberrant mRNA translation is a hallmark of carcinogenesis, impacting proteins crucial for tumor development.
- Eukaryotic initiation factor eIF4E regulates translation of cancer-related transcripts; its altered expression is linked to various cancers and reduced patient survival.
Purpose of the Study:
- To investigate the association between eIF4E protein levels and breast tumor characteristics.
- To evaluate the prognostic significance of eIF4E expression on patient survival, considering adjuvant chemotherapy.
- To explore eIF4E's potential as a predictive marker for anthracycline chemotherapy response.
Main Methods:
- Immunohistochemistry (IHC) was used to quantify eIF4E protein levels in 1,233 breast tumor samples.
- Tissue microarrays were utilized for high-throughput analysis.
- Statistical analyses, including multivariate analysis and subgroup analysis by chemotherapy treatment, were performed.
Main Results:
- High eIF4E expression was significantly associated with aggressive tumor features: higher grade, receptor negativity (ER, PR), HER2 positivity, elevated p53 and Ki67, and triple-negative subtype.
- Elevated eIF4E levels predicted worse breast cancer-specific survival (HR=1.99) and were an independent prognostic factor.
- The survival impact of high eIF4E was most pronounced in patients treated with anthracycline chemotherapy (HR=3.34), with no significant effect in non-anthracycline treated groups.
Conclusions:
- High eIF4E protein expression is linked to adverse breast cancer characteristics and predicts poor survival.
- eIF4E expression may serve as a predictive biomarker for anthracycline chemotherapy efficacy.
- Further research is warranted to explore eIF4E's role as a therapeutic target and predictive factor.
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