A Novel Approach to Increase Breast Cancer Chemosensitivity: Disruption of the Anti-Apoptotic Function of Translation Factor eIF4E
Abstract
In this report we present data in support of Aim 1 of our project. Utilizing human breast carcinoma cell lines as an in vitro model for naturally occurring malignancy, we demonstrated that both the apoptotic and translational machinery are activated in five breast carcinoma cell lines. Suppression of cap-dependent translation by pharmacological inhibitors of 4E-BPl phosphorylation or by ectopic expression of 4E-BPl stimulated apoptosis and abrogated chemoresistance in fibroblasts and breast carcinoma cells expressing oncogenic Ras. Activation of apoptosis by translational inhibitors paralleled their ability to repress the cap-dependent translation apparatus. These results show that the integrity of the cap-dependent translational apparatus is critically important for breast cancer cell chemoresistance. They also suggest that targeted disruption of the cap-binding complex can be used as a novel approach for blocking malignant progression in breast carcinoma and other tumors whose growth depends on activation of cap-dependent translation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA389261
Entities
People
- Vitaly A. Polunovsky
Organizations
- University of Minnesota