eIF4E expression in tumors: its possible role in progression of malignancies

摘要: A central issue in the study of neoplastic transformation is to understand how proto-oncogene products deregulate normal processes cell growth and differentiation: an intrinsic aspect this probe sequence events leading altered expression proto-oncogenes. In past few years, studies aimed at understanding regulation function protein synthesis initiation factors, eIF4E initially, culminated unexpected finding that a moderate overexpression factor results dramatic phenotypic changes, including rapid proliferation malignant transformation. Conversely, tumorigenic properties cancer cells can be strongly inhibited by antisense-RNA against eIF4E, or inhibitory proteins: 4E-BPs. Furthermore, elevated carcinomas breast, head neck (HNSCC) prostate, but not typical benign lesions. This strong indication may mark critical transition progression. Establishing greater output necessary step for order sustain their proliferation. However, analysis transformed revealed only proteins was greatly enhanced, while most minimally increased. One possible explanation causes these effects specifically increasing translational efficiency several oncogene transcripts, products. The feasibility hypothesis confirmed experimentally with identification important are upregulated eIF4E-overexpressing cells. These include: c-Myc, cyclin DI ODC, which control cycle progression tumorigenesis; basic fibroblast (FGF-2) vascular endothelial (VEGF), powerful promoters angiogenesis. deeper mRNAs dependent on excess eIF4E/F efficient translation will eventually result fuller fundamental role different pathophysiological conditions, malignancy.