{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:27:35Z","timestamp":1783592855410,"version":"3.55.0"},"reference-count":44,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Increased levels of vascular endothelial growth factor (VEGF) are associated with a poor response of breast cancer to anti-hormone treatment. Although VEGF is regarded as an endothelial-specific growth factor, recent reports have shown that VEGF can promote proliferation of other cell types, including breast tumor cells. We have characterized the proliferative effects of VEGF in breast cancer cell lines that are commonly used for understanding the role of estrogens, progestins, and anti-hormones on tumor growth. Since steroid hormones can increase the level of VEGF in certain breast cancer cells, we evaluated the effects of exogenous VEGF on the growth-suppressive effects of anti-estrogen (ICI 182,780) and RU-486 (anti-progestin mifepristone) in human breast cancer cells. VEGF165 and VEGF121 increased the proliferation of tumor cell lines that expressed VEGFR-2 (VEGF receptor 2) (flk\/kdr) via the extracellular signal-regulated kinase\/mitogen activated protein kinase (ERK\/MAPK) pathway. Furthermore, VEGF induced the expression of the anti-apoptotic protein Bcl-2 and blocked down-regulation of Bcl-2 by ICI 182,780 and induced Bcl-2 in BT-474 and T47-D cells even in the presence of RU-486. Increased Bcl-2 levels in response to VEGF were associated with increased proliferation and survival of tumor cells even in the presence of anti-hormones. These results suggest that VEGF stimulates proliferation of VEGFR2-positive tumor cells, promotes survival via the expression and activity of Bcl-2 and overrides the growth-suppressive effects of anti-hormones. This represents a potential explanation for anti-hormone resistance and tumor progression in clinical samples. Thus, it may be useful to use combined modality treatment involving anti-hormones and anti-angiogenic agents to treat breast cancers that express elevated levels of VEGF.<\/jats:p>","DOI":"10.1677\/erc.1.01221","type":"journal-article","created":{"date-parts":[[2006,9,5]],"date-time":"2006-09-05T15:13:24Z","timestamp":1157469204000},"page":"905-919","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":117,"title":["Vascular endothelial growth factor induces proliferation of breast cancer cells and inhibits the anti-proliferative activity of anti-hormones"],"prefix":"10.1530","volume":"13","author":[{"given":"Yayun","family":"Liang","sequence":"first","affiliation":[{"name":"1Dalton Cardiovascular Research Center, University of Missouri, 134 Research Park Drive, Columbia, Missouri 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf A","family":"Brekken","sequence":"additional","affiliation":[{"name":"2Hamon Center for Therapeutic Oncology Research and Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman M","family":"Hyder","sequence":"additional","affiliation":[{"name":"1Dalton Cardiovascular Research Center, University of Missouri, 134 Research Park Drive, Columbia, Missouri 65211, USA"},{"name":"3Biomedical Sciences, University of Missouri, Columbia, Missouri 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2026070906015346200_ALI-AND-COOMBES-2000","doi-asserted-by":"crossref","unstructured":"Ali\n            S\n           & Coombes RC 2000 Estrogen receptor alpha in human breast cancer: occurrence and significance. 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