| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Endocrinology |
and ß1
Institut National de la Santé et de la Recherche Médicale U553, IFR 105 Institut d’Hématologie Paris 7, Hôpital Saint Louis, 75475 Paris Cedex 10, France [H. B-L., M. A., M. P-A.]; U327, Faculté de Médecine Xavier Bichat, 75870 Paris Cedex 18, France [B. L.]; and CNRS-UMR 6543, Centre de Biochimie, Université de Nice, 06108 Nice, France [J. M.]
Vascular endothelial growth factor (VEGF) is a potent angiogenic and prognostic factor for many tumors, including those of endocrine-responsive tissues such as the breast and uterus. Recent studies indicate that 17ß-estradiol (E2) modulates VEGF expression in breast and uterine cells, involving transcriptional activation through estrogen receptor (ER) 
. However, molecular mechanisms of VEGF regulation mediated by the two ER subtypes and the potential role of ERß in the control of breast cancer angiogenesis have not yet been investigated. In transient transfection assays using the VEGF(-2275/+54) promoter-luciferase construct, E2 (1 nM) increased transcription activity in MCF-7 cells (either untransfected or cotransfected with ER) and it increased transcription activity in MDA-MB-231 cells cotransfected with ER or ERß (1.8- and 2-fold induction, respectively). The positive effect was abolished when MCF-7 cells were treated with pure antiestrogen ICI 182,780 or the agonist/antagonist tamoxifen (1 µM). To identify response elements involved in this transcriptional regulation, MCF-7 or MDA-MB-231 cells were transfected with several deletion constructs of the VEGF promoter. Deletion of 1.2–2.3 kb upstream to the transcription start in the VEGF promoter abrogated E2-dependent transcription in these cells. This region contains an imperfect estrogen-responsive element (ERE), ERE1520, and one activator protein 1 site. Transfection of MCF-7 cells (ER) with the ERE1520-luciferase construct conferred transcriptional activity with 1 nM E2 (1.9-fold induction). Also, the imperfect ERE formed a complex with ER or ERß proteins in gel shift assay using MCF-7 or MDA-MB-231 nuclear extracts. In contrast to ER, ERß could transactivate VEGF reporter construct in MDA-MB-231 cells, in the presence of E2 or tamoxifen, suggesting different transactivational mechanisms between ER and ERß in the presence of tamoxifen. Interestingly, E2 inhibited VEGF transcription in MCF-7 cells transfected with ERß or MDA-MB-231 cells cotransfected with ER and ERß, suggesting that heterodimerization of ER/ERß has the ability to inhibit E2-induced VEGF expression in breast cancer cells. These results demonstrate that VEGF is a target gene for ER and ERß in breast cancer cells; it remains to be determined whether ER and ERß expression in breast biopsies correlates with VEGF expression and vascular density.
This article has been cited by other articles:
|
|
 |
|
  M. Dadiani, D. Seger, T. Kreizman, D. Badikhi, R. Margalit, R. Eilam, and H. Degani Estrogen regulation of vascular endothelial growth factor in breast cancer in vitro and in vivo: the role of estrogen receptor {alpha} and c-Myc Endocr. Relat. Cancer, September 1, 2009; 16(3): 819 - 834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Atsriku, D. J. Britton, J. M. Held, B. Schilling, G. K. Scott, B. W. Gibson, C. C. Benz, and M. A. Baldwin Systematic Mapping of Posttranslational Modifications in Human Estrogen Receptor-{alpha} with Emphasis on Novel Phosphorylation Sites Mol. Cell. Proteomics, March 1, 2009; 8(3): 467 - 480. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. N. Taylor, Jie Yu, P. B. Torres, A. C. Schickedanz, J. K. Park, M. D. Mueller, and N. Sidell Mechanistic and Therapeutic Implications of Angiogenesis in Endometriosis Reproductive Sciences, February 1, 2009; 16(2): 140 - 146. [Abstract] [PDF]
|
|
|
|
 |
|
 K. Guo, V. Gokhale, L. H. Hurley, and D. Sun Intramolecularly folded G-quadruplex and i-motif structures in the proximal promoter of the vascular endothelial growth factor gene Nucleic Acids Res., August 1, 2008; 36(14): 4598 - 4608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Holmes, J. C. Huang, T. R. Pace, A. B. Howard, and H. B. Muss Tamoxifen and Aromatase Inhibitors Differentially Affect Vascular Endothelial Growth Factor and Endostatin Levels in Women with Breast Cancer Clin. Cancer Res., May 15, 2008; 14(10): 3070 - 3076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Banerjee, S. Pancholi, R. A'Hern, Z. Ghazoui, I. E. Smith, M. Dowsett, and L.-A. Martin The Effects of Neoadjuvant Anastrozole and Tamoxifen on Circulating Vascular Endothelial Growth Factor and Soluble Vascular Endothelial Growth Factor Receptor 1 in Breast Cancer Clin. Cancer Res., May 1, 2008; 14(9): 2656 - 2663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Buteau-Lozano, G. Velasco, M. Cristofari, P. Balaguer, and M. Perrot-Applanat Xenoestrogens modulate vascular endothelial growth factor secretion in breast cancer cells through an estrogen receptor-dependent mechanism J. Endocrinol., February 1, 2008; 196(2): 399 - 412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-A. Herve, H. Buteau-Lozano, R. Vassy, I. Bieche, G. Velasco, M. Pla, G. Perret, S. Mourah, and M. Perrot-Applanat Overexpression of Vascular Endothelial Growth Factor 189 in Breast Cancer Cells Leads to Delayed Tumor Uptake with Dilated Intratumoral Vessels Am. J. Pathol., January 1, 2008; 172(1): 167 - 178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hartman, K. Lindberg, A. Morani, J. Inzunza, A. Strom, and J.-A. Gustafsson Estrogen Receptor {beta} Inhibits Angiogenesis and Growth of T47D Breast Cancer Xenografts Cancer Res., December 1, 2006; 66(23): 11207 - 11213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hamada, M. K. Kim, A. Iwakura, M. Ii, T. Thorne, G. Qin, J. Asai, Y. Tsutsumi, H. Sekiguchi, M. Silver, et al. Estrogen Receptors {alpha} and {beta} Mediate Contribution of Bone Marrow-Derived Endothelial Progenitor Cells to Functional Recovery After Myocardial Infarction Circulation, November 21, 2006; 114(21): 2261 - 2270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S M Hyder Sex-steroid regulation of vascular endothelial growth factor in breast cancer. Endocr. Relat. Cancer, September 1, 2006; 13(3): 667 - 687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kim, M. Kaneko, K. Arihiro, M. Emi, K. Tanabe, S. Murakami, A. Osaki, and K. Inai Extranuclear expression of hormone receptors in primary breast cancer Ann. Onc., August 1, 2006; 17(8): 1213 - 1220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Higgins, S. Liu, M. Abdelrahim, K. Yoon, K. Vanderlaag, W. Porter, R. P. Metz, and S. Safe Vascular Endothelial Growth Factor Receptor-2 Expression Is Induced by 17{beta}-Estradiol in ZR-75 Breast Cancer Cells by Estrogen Receptor {alpha}/Sp Proteins Endocrinology, July 1, 2006; 147(7): 3285 - 3295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Cherradi, C. Lejczak, A. Desroches-Castan, and J.-J. Feige Antagonistic Functions of Tetradecanoyl Phorbol Acetate-Inducible-Sequence 11b and HuR in the Hormonal Regulation of Vascular Endothelial Growth Factor Messenger Ribonucleic Acid Stability by Adrenocorticotropin Mol. Endocrinol., April 1, 2006; 20(4): 916 - 930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Kazi, J. M. Jones, and R. D. Koos Chromatin Immunoprecipitation Analysis of Gene Expression in the Rat Uterus in Vivo: Estrogen-Induced Recruitment of Both Estrogen Receptor {alpha} and Hypoxia-Inducible Factor 1 to the Vascular Endothelial Growth Factor Promoter Mol. Endocrinol., August 1, 2005; 19(8): 2006 - 2019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Wood, K. Bove, S. You, A. Chambers, and W. J.M. Hrushesky Cancer growth and spread are saltatory and phase-locked to the reproductive cycle through mediators of angiogenesis Mol. Cancer Ther., July 1, 2005; 4(7): 1065 - 1075. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Pages and J. Pouyssegur Transcriptional regulation of the Vascular Endothelial Growth Factor gene-a concert of activating factors Cardiovasc Res, February 15, 2005; 65(3): 564 - 573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang, N. Wakisaka, C. C Tomlinson, S. M DeWire, S. Krall, J. S Pagano, and B. Damania The Kaposi's Sarcoma-Associated Herpesvirus (KSHV/HHV-8) K1 Protein Induces Expression of Angiogenic and Invasion Factors Cancer Res., April 15, 2004; 64(8): 2774 - 2781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wu, J. Richer, K. B. Horwitz, and S. M. Hyder Progestin-Dependent Induction of Vascular Endothelial Growth Factor in Human Breast Cancer Cells: Preferential Regulation by Progesterone Receptor B Cancer Res., March 15, 2004; 64(6): 2238 - 2244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Tangkeangsirisin, J. Hayashi, and G. Serrero PC Cell-Derived Growth Factor Mediates Tamoxifen Resistance and Promotes Tumor Growth of Human Breast Cancer Cells Cancer Res., March 1, 2004; 64(5): 1737 - 1743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, R. J. Traystman, P. D. Hurn, and M. M. Wang Membrane Restraint of Estrogen Receptor {alpha} Enhances Estrogen-Dependent Nuclear Localization and Genomic Function Mol. Endocrinol., January 1, 2004; 18(1): 86 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Guo, Q. Fang, H.-Q. Tao, C. A. Schafer, B. M. Fenton, I. Ding, B. Hu, and S.-Y. Cheng Overexpression of Vascular Endothelial Growth Factor by MCF-7 Breast Cancer Cells Promotes Estrogen-independent Tumor Growth in Vivo Cancer Res., August 1, 2003; 63(15): 4684 - 4691. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
