Expression levels of eIF4E, VEGF, and cyclin D1, and correlation of eIF4E with VEGF and cyclin D1 in multi-tumor tissue microarray.

The mRNA cap-binding protein, eukaryotic initiation factor 4E (eIF4E), is a rate-limiting factor of cap-dependent translation initiation. When elevated, eIF4E greatly facilitates translation of a selected spectrum of mRNAs coding for proteins critical to angiogenesis and growth such as vascular endothelial growth factor (VEGF) and cyclin D1. Expression levels of eIF4E, VEGF, and cyclin D1 were examined in multi-tumor tissue microarray by immunohistochemistry and analyzed quantitatively. eIF4E, VEGF and cyclin D1 protein were elevated in tumors of the breast (62, 78, or 40%), colon (72, 77, or 12%), glioblastoma multiforme (48, 68, or 52%), lymphoma (66, 74, or 38%), melanoma (59, 73, or 58%), NSCLC (81, 82, or 29%), ovary (50, 39, or 13%), and prostate (78, 97, or 21%), respectively. eIF4E levels were strongly correlated with VEGF and cyclin D1 in melanoma (Spearman's r=0.97 and 0.77; all P<0.0001); moderately in tumors of the breast (r=0.55 and 0.41; all P<0.0005), colon (0.63 and 0.56; all P<0.0001), lung (0.53 and 0.53; all P<0.005), lymphoma (0.50 and 0.61; all P<0.0005), prostate (0.46 and 0.54; all P<0.005), or ovary (0.56 and 0.46; all P<0.005); and weakly in tumors of glioblastoma multiforme (r=0.20 and 0.31; all P>0.15). The significant association of eIF4E with VEGF and cyclin D1 in multiple tumors supports a role for eIF4E in translational regulation of proteins related to angiogenesis and growth.