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 apoptosis 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 endothelial cells, preventing apoptosis by inducing Bcl-2 expression. In both murine (4T1) and human (MDA-MB-231) metastatic mammary carcinoma cell lines, we found that VEGF upregulated Bcl-2 expression and anti-VEGF antibodies reduced 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 induced apoptosis directly in tumour cells. Therefore, in addition to its role in angiogenesis and vessel permeability, VEGF acts as a survival factor for tumour cells, inducing Bcl-2 expression and inhibiting tumour cell apoptosis.
Pidgeon
G P
GP
Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Beaumont, Dublin 9, Ireland.
Barr
M P
MP
Harmey
J H
JH
Foley
D A
DA
Bouchier-Hayes
D J
DJ
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000502:physiology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008222:Lymphokines / Q000502:physiology*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors