Abstract
Alteration of the phenotype of breast cancers from estrogen-dependent to estrogen-independent growth often leads to the failure of antiestrogenic tumor therapies. We report that overexpression of vascular endothelial growth factor (VEGF) by estrogen-dependent MCF-7 breast cancer cells could abolish estrogen-dependent tumor growth in ovariectomized mice. In the absence of estrogen, MCF-7 VEGF-expressing tumors with increased vessel density showed growth kinetics similar to, or even greater than, that of parental MCF-7 tumors with estrogen supplementation. Overexpression of VEGF by MCF-7 cells or treatment on parental MCF-7 cells with recombinant VEGF also stimulated cell proliferation in culture. Our data suggest that VEGF stimulation of MCF-7 tumor angiogenesis and growth is mediated by both autocrine and paracrine mechanisms.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Breast Neoplasms / blood supply
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology*
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Cell Division / drug effects
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Cell Division / physiology
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Endothelial Growth Factors / biosynthesis*
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Endothelial Growth Factors / genetics
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Estradiol / pharmacology*
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Female
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Humans
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Intercellular Signaling Peptides and Proteins / biosynthesis*
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Intercellular Signaling Peptides and Proteins / genetics
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Lac Operon
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Lymphokines / biosynthesis*
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Lymphokines / genetics
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Mice
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Mice, Nude
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Neoplasms, Hormone-Dependent / blood supply
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Neoplasms, Hormone-Dependent / genetics
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Neoplasms, Hormone-Dependent / metabolism
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Neoplasms, Hormone-Dependent / pathology
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Neovascularization, Pathologic / genetics
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Neovascularization, Pathologic / metabolism
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Protein Isoforms
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Receptors, Vascular Endothelial Growth Factor / biosynthesis
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Transfection
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Tumor Cells, Cultured
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Endothelial Growth Factors
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Intercellular Signaling Peptides and Proteins
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Lymphokines
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Protein Isoforms
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Estradiol
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Receptors, Vascular Endothelial Growth Factor