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Vascular Endothelial Growth Factor (VEGF) Receptor Inhibitors, SU11248 and SU5416, Directly Inhibit the Proliferation of Cultured ER‐positive and ER‐negative Human Breast Cancer Cells
Author(s) -
Wells Jeremy,
Young Emily,
Tucker Kevan,
Chawla Simran,
Gu JianWei
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.984.3
Subject(s) - autocrine signalling , cancer cell , breast cancer , cancer research , vascular endothelial growth factor , paracrine signalling , cancer , chemistry , receptor , endocrinology , biology , medicine , vegf receptors
The autocrine effects of VEGF on cancer cells are poorly understood. Present study determines if VEGF and its receptor are differentially expressed in ER‐positive (MCF‐7) and ER‐negative (MDA‐MB‐231) human breast cancer cells, and if VEGF receptor (VEGFR) inhibitors, SU11248 and SU5416, directly decrease the proliferation of those human breast cancer cells. MCF‐7 and MDA‐MB‐231 cells were cultured using RPMI 1640 media with 10% FBS. β‐estradiol increased VEGF expression in MCF‐7 cells (1762±56 vs.1136±58 pg/mg, P<0.01) but not in MDA‐MB‐231 cells. ELISA showed that VEGF and VEGFR‐2 were more highly expressed in ER‐negative cells than ER‐positive cells (>8‐fold, P<0.01). 3H‐thymidine incorporation showed that SU11248 (10 µmol/L) caused both a 77% and 75% decrease, and SU5416 (10 µmol/L) caused both a 56% and 36% decrease in the proliferations of MCF‐7 and MDA‐MB‐231 cells, respectively, compared to the control (P<0.01). The results indicate that VEGF and VEGFR are differentially expressed in ER‐positive and ‐negative breast cancer cells, and that SU11248 exerted a stronger effect than SU5416 on inhibiting the proliferation of both ER‐positive and negative human breast cancer cells. These findings support the hypothesis that VEGFR inhibitors, as an anti‐angiogenic therapy, also target the autocrine effects of VEGF to suppress both ER‐positive and ‐negative breast cancer progression. (HL51971 & AA013821)