Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells.
The expression of vascular endothelial growth factor (VEGF) by breast tumors has been previously correlated with a poor prognosis in the pathogenesis of breast cancer. Furthermore, VEGF secretion is a prerequisite for tumor development. Although most of the effects of VEGF have been shown to be attributable to the stimulation of endothelial cells, we present evidence here that breast tumor cells are capable of responding to VEGF. We show that VEGF stimulation of T-47D breast cancer cells leads to changes in cellular signaling and invasion. VEGF increases the cellular invasion of T-47D breast cancer cells on Matrigel/ fibronectin-coated transwell membranes by a factor of two. Northern analysis for the expression of the known VEGF receptors shows the presence of moderate levels of Flt-1 and low levels of Flk-1/KDR mRNAs in a variety of breast cancer cell lines. T-47D breast cancer cells bind 125I-labeled VEGF with a Kd of 13 x 10(-9) M. VEGF induces the activation of the extracellular regulated kinases 1,2 as well as activation of phosphatidylinositol 3'-kinase, Akt, and Forkhead receptor L1. These findings in T-47D breast cancer cells strongly suggest an autocrine role for VEGF contributing to the tumorigenic phenotype.
Price
D J
DJ
Division of Experimental Medicine, Beth Israel-Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA.
Miralem
T
T
Jiang
S
S
Steinberg
R
R
Avraham
H
H
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D016228:Endothelial Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D000072179:Interleukin-1 Receptor-Like 1 Protein; D007797:Laminin / Q000494:pharmacology; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology*; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D020890:Neuregulin-1 / Q000378:metabolism / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor / Q000187:drug effects / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D004338:Drug Combinations; D016228:Endothelial Growth Factors; D005353:Fibronectins; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D007797:Laminin; D008222:Lymphokines; D008565:Membrane Proteins; D020890:Neuregulin-1; D011506:Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C059485:matrigel; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D020928:Mitogen-Activated Protein Kinases