title: Tumor growth enhancing effects of vascular endothelial growth factor are associated with increased nitric oxide synthase activity and inhibition of apoptosis in human breast carcinoma xenografts.
abstract: Previously, we demonstrated the significance of vascular endothelial growth factor (VEGF) in promoting the growth of tetracycline-regulated human VEGF165 retroviral vector transduced T47-D breast carcinoma cells, particularly at the early stages of tumor development (Cancer Res. 57 (1997) 3924). Here, we showed histologically that the VEGF overexpressing (VEGF (+)) T47-D cells formed a distinct tumor nodule at day 11, while control cells showed no evidence of replication. The VEGF (+) tumors contained large avascular cavities at days 11 and 21, which were replaced by basement membrane-lined channels at day 30. The number of proliferating tumor cells was not significantly different between the VEGF (+) and control tumors, but the number of apoptotic cells was significantly decreased in the VEGF (+) tumors. Increased nitric oxide synthase (NOS) activity was also observed in the VEGF (+) tumors. These findings indicate that VEGF contributes to tumor growth through inhibition of apoptosis and increased NOS activity, which may be critical during pre-vascular stages of tumor development.
authors.affiliation: Tumor Biology and Carcinogenesis Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Harris
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Schoeffner
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshiji
authors.forename: Unnur P
authors.initials: UP
authors.lastname: Thorgeirsson
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002455:Cell Division; D016228:Endothelial Growth Factors / Q000502:physiology*; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008222:Lymphokines / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012190:Retroviridae / Q000235:genetics; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D009569:Nitric Oxide; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse