Vascular endothelial growth factor (VEGF) upregulates BCL-2 and inhibits apoptosis in human and murine mammary adenocarcinoma cells

Tumour progression is regulated by the balance of proliferation and apoptos is in the tumour cell population. To date, the role of vascular endothelial growth factor (VEGF) in tumour growth has been attributed to the induction of angiogenesis. VEGF has been shown to be a survival factor for endotheli al cells, preventing apoptosis by inducing Bcl-2 expression. In both murine (4T1) and human (MDA-MB-231) metastatic mammary carcinoma cell lines, we f ound that VEGF upregulated Bcl-2 expression and anti-VEGF antibodies reduce d Bcl-2 expression. These alterations in Bcl-2 expression were reflected by the levels of tumour cell apoptosis. VEGF resulted in reduced tumour cell apoptosis, whereas its inhibition with anti-VEGF neutralizing antibodies in duced apoptosis directly in tumour cells. Therefore, in addition to its rol e in angiogenesis and vessel permeability, VEGF acts as a survival factor f or tumour cells, inducing Bcl-2 expression and inhibiting tumour cell apopt osis. (C) 2001 Cancer Research Campaign.