VASCULAR ENDOTHELIAL GROWTH-FACTOR IS ESSENTIAL FOR INITIAL BUT NOT CONTINUED IN-VIVO GROWTH OF HUMAN BREAST-CARCINOMA CELLS

In this study, we used a self-contained tetracycline-regulated retrovi ral vector system to elucidate the role of vascular endothelial growth factor (VEGF) in controlling s.c. growth of human T-47D breast carcin oma cells. VEGF expression was tightly regulated by this system, both in vitro and in nude mouse xenografts. A 2.4-fold increase in tumor vo lume was associated with VEGF overexpression. Tumor growth was almost completely inhibited when VEGF was suppressed from the time of T-47D c ell inoculation, and a 6-fold reduction in tumor volume was observed w hen VEGF suppression was started in 175-mm(3) tumors, However, no grow th inhibition was observed when VEGF suppression was started in 820-mm (3) tumors, In these tumors, basic fibroblast growth factor and transf orming growth factor alpha RNA expression was detected after VEGF was switched off. These findings demonstrate that VEGF is critical for the initial ss. growth of T-47D breast carcinoma cells, whereas other ang iogenic factors can compensate for the loss of VEGF after the tumors h ave reached a certain size.