DIFFERENTIAL EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR MESSENGER-RNA VS PROTEIN ISOFORM EXPRESSION IN HUMAN BREAST-CANCER AND RELATIONSHIP TO EIF-4E

Angiogenesis is the formation of new blood vessels from the existing v asculature. Vascular endothelial growth factor (VEGF) is an endotheliu m-specific angiogenic factor strongly implicated in pathological angio genesis. In this study, the mRNA and protein expression of the four al ternatively spliced VEGF isoforms (121, 165, 189 and 206 amino acids) were examined in normal and malignant breast tissues. Three VEGF trans cripts were detected in both (121>165>189), whereas only VEGF165 prote in was detected. The tumours expressed more VEGF mRNA (P = 0.02) and p rotein (P < 0.0001), with eight-fold more VEGF protein generated per m RNA unit (P = 0.009). To examine this further, the expression of elF-4 E, a translation initiation factor, was examined. Increased elF-4E mRN A levels were detected in the rumours (P < 0.0001) that correlated wit h VEGF mRNA (P = 0.0002), implying co-regulation of these genes. VEGF mRNA expression was elevated in tumours expressing the epidermal growt h factor receptor (P < 0.01), but there was no difference according to oestrogen receptor status (P = 0.9), node status (P = 0.09) or betwee n differing histologies (P = 0.4). These data suggest that elevated VE GF protein expression, by both enhanced transcription and translation, is a potential means by which tumour angiogenesis is induced in breas t carcinomas. VEGF expression is also significantly associated with fa ctors correlating with a poor outcome, implying a role in progression of this disease.