Hormonal regulation of VEGF in orthotopic MCF7 human breast cancer.
Vascular endothelial growth factor (VEGF) mRNA and protein levels were higher in MCF7 breast cancer cells and orthotopic tumors after treatment with tamoxifen, as compared with treatment with estrogen. Accordingly, tumor vascular permeability, evaluated in vivo from contrast-enhanced magnetic resonance imaging, was elevated during treatment with tamoxifen. The results indicate that estrogen regulates angiogenesis in MCF7 tumors by maintaining VEGF at levels sufficient for the generation of functional microcapillaries and consequently facilitates tumor growth. During tamoxifen treatment, estrogen regulation is removed, and VEGF increases to levels that enhance markedly vascular permeability and reduce their perfusion function, leading to inhibition of tumor progression.
Bogin
Liora
L
Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100 Israel.
Degani
Hadassa
H
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D003287:Contrast Media; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000493:pharmacokinetics*; D019786:Gadolinium DTPA; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D008279:Magnetic Resonance Imaging; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018931:Antineoplastic Agents, Hormonal; D003287:Contrast Media; D016228:Endothelial Growth Factors; D004965:Estrogen Antagonists; D004967:Estrogens; D008222:Lymphokines; D020033:Protein Isoforms; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013629:Tamoxifen; D019786:Gadolinium DTPA