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Overexpression of Vascular Endothelial Growth Factor by MCF-7 Breast Cancer Cells Promotes Estrogen-independent Tumor Growth in Vivo¹

University of Pittsburgh Cancer Institute and Department of Pathology [P. G., Q. F., H-Q. T., C. A. S., S-Y. C.] and Medicine [B. H.], Research Pavilion at Hillman Cancer Center, Pittsburgh, Pennsylvania 15213-1863, and University of Rochester Cancer Center and Department of Radiation Oncology, Rochester, New York 14642 [B. M. F., I. D.]

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.

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