| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Endocrinology |
Department of Integrative Biology and Pharmacology, University of Texas Health Sciences Center, Houston, Texas 77030 [S. M. H., C. C., G. M. S.], and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030 [Z. N.]
Vascular endothelial growth factor (VEGF) is a potent stimulator of
angiogenesis and a prognostic factor for many tumors including those of
endocrine-responsive tissues such as the breast and uterus. We and
others have previously shown that VEGF is regulated by estradiol and
tamoxifen in the uterus and by estradiol in human breast cancer cells,
and pharmacological evidence has suggested that this regulation was
mediated by transcriptional activation of the estrogen receptor (ER).
This prompted us to investigate whether the VEGF gene contains
sequences that bind the ER and confer hormonal inducibility to reporter
constructs in the presence of the two ER subtypes. These studies
identified two sequences homologous to the consensus estrogen response
element, GGTCAnnnTGACC, which bind both ER-
and ER-ß. One of these
elements is located in the 5'-untranslated region of the VEGF gene
(GGGCAaagTGACT), and the other is located
in the 3'-untranslated region
(GAGCAcccTGCCC). Competition with excess
unlabeled oligonucleotides indicates that these two elements
bind both ERs specifically, mutations in either half-site of the two
elements abolish receptor binding, and ER-- and ER-ß-specific
antibodies interact with complexes formed with the corresponding
receptor subtypes. In cells containing either ER- or ER- ß, the
3'-element behaves as a traditional enhancer that confers hormone
inducibility to reporter constructs in an orientation-independent
manner, and transcriptional activity is blocked by the pure
antiestrogen ICI 182,780. The pattern of transcriptional activity of
the element located in the 5'-flanking region is more complex. In the
orientation found in the endogenous gene, this element is nonresponsive
to ER-ß but confers estrogen-dependent inhibition of transcription
with ER- that is blunted by ICI 182,780. In the opposite
orientation, the 5'-element confers hormone inducibility with either
ER- or -ß, and ICI 182,780 blocks activation by ER- but
not by ER-ß. These findings support the hypotheses that estrogens
directly regulate VEGF transcription in target tissues and tumors,
although such regulation appears likely to involve a complex interplay
of cis- and trans-acting elements not
previously observed for other hormone-responsive genes.
This article has been cited by other articles:
|
|
 |
|
  S. Bake, L. Ma, and F. Sohrabji Estrogen Receptor-{alpha} Overexpression Suppresses 17{beta}-Estradiol-Mediated Vascular Endothelial Growth Factor Expression and Activation of Survival Kinases Endocrinology, August 1, 2008; 149(8): 3881 - 3889. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. van den Driesche, V. M Smith, M. Myers, and W C. Duncan Expression and regulation of oestrogen receptors in the human corpus luteum Reproduction, April 1, 2008; 135(4): 509 - 517. [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]
|
|
|
|
|
|
V L Bosquiazzo, J G Ramos, J Varayoud, M Munoz-de-Toro, and E H Luque Mast cell degranulation in rat uterine cervix during pregnancy correlates with expression of vascular endothelial growth factor mRNA and angiogenesis Reproduction, May 1, 2007; 133(5): 1045 - 1055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bergman Jungestrom, L. U. Thompson, and C. Dabrosin Flaxseed and Its Lignans Inhibit Estradiol-Induced Growth, Angiogenesis, and Secretion of Vascular Endothelial Growth Factor in Human Breast Cancer Xenografts In vivo Clin. Cancer Res., February 1, 2007; 13(3): 1061 - 1067. [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]
|
|
|
|
 |
|
 F. Bussolino Small Molecule Approaches for Promoting Ischemic Tissue Vascularization Circ. Res., August 4, 2006; 99(3): 231 - 233. [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]
|
|
|
|
 |
|
 R. C. Bott, R. M. McFee, D. T. Clopton, C. Toombs, and A. S. Cupp Vascular Endothelial Growth Factor and Kinase Domain Region Receptor Are Involved in Both Seminiferous Cord Formation and Vascular Development During Testis Morphogenesis in the Rat Biol Reprod, July 1, 2006; 75(1): 56 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Pietras Biologic Basis of Sequential and Combination Therapies for Hormone-Responsive Breast Cancer Oncologist, July 1, 2006; 11(7): 704 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Doi, E. Noiri, A. Nakao, T. Fujita, S. Kobayashi, and K. Tokunaga Functional Polymorphisms in the Vascular Endothelial Growth Factor Gene Are Associated with Development of End-Stage Renal Disease in Males J. Am. Soc. Nephrol., March 1, 2006; 17(3): 823 - 830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Dabrosin Positive Correlation between Estradiol and Vascular Endothelial Growth Factor but not Fibroblast Growth Factor-2 in Normal Human Breast Tissue In vivo Clin. Cancer Res., November 15, 2005; 11(22): 8036 - 8041. [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]
|
|
|
|
 |
|
 R. D. KOOS, A. A. KAZI, M. S. ROBERSON, and J. M. JONES New Insight into the Transcriptional Regulation of Vascular Endothelial Growth Factor Expression in the Endometrium by Estrogen and Relaxin Ann. N.Y. Acad. Sci., May 1, 2005; 1041(1): 233 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. L. RYAN, R. C. YOUNGBLOOD, J. HARVILL, and S. T. WILLARD Photonic Monitoring in Real Time of Vascular Endothelial Growth Factor Receptor 2 Gene Expression under Relaxin-Induced Conditions in a Novel Murine Wound Model Ann. N.Y. Acad. Sci., May 1, 2005; 1041(1): 398 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Soares, G. Balogh, S. Guo, F. Gartner, J. Russo, and F. Schmitt Evidence for the Notch Signaling Pathway on the Role of Estrogen in Angiogenesis Mol. Endocrinol., September 1, 2004; 18(9): 2333 - 2343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. O'Lone, M. C. Frith, E. K. Karlsson, and U. Hansen Genomic Targets of Nuclear Estrogen Receptors Mol. Endocrinol., August 1, 2004; 18(8): 1859 - 1875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M J Currie, V Hanrahan, S P Gunningham, H R Morrin, C Frampton, C Han, B A Robinson, and S B Fox Expression of vascular endothelial growth factor D is associated with hypoxia inducible factor (HIF-1{alpha}) and the HIF-1{alpha} target gene DEC1, but not lymph node metastasis in primary human breast carcinomas J. Clin. Pathol., August 1, 2004; 57(8): 829 - 834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Dey, H. Lim, S. K. Das, J. Reese, B. C. Paria, T. Daikoku, and H. Wang Molecular Cues to Implantation Endocr. Rev., June 1, 2004; 25(3): 341 - 373. [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]
|
|
|
|
|
|
S. Garvin and C. Dabrosin Tamoxifen Inhibits Secretion of Vascular Endothelial Growth Factor in Breast Cancer in Vivo Cancer Res., December 15, 2003; 63(24): 8742 - 8748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. Fertuck, J. E. Eckel, C. Gennings, and T. R. Zacharewski Identification of temporal patterns of gene expression in the uteri of immature, ovariectomized mice following exposure to ethynylestradiol Physiol Genomics, October 17, 2003; 15(2): 127 - 141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. Turner, A. L. Harris, S. Melmed, and J. A. H. Wass Angiogenesis in Endocrine Tumors Endocr. Rev., October 1, 2003; 24(5): 600 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Gagne, M. Page, G. Robitaille, P. Hugo, and D. Gosselin Levels of vascular endothelial growth factor (VEGF) in serum of patients with endometriosis Hum. Reprod., August 1, 2003; 18(8): 1674 - 1680. [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]
|
|
|
|
|
|
C. E. Murphy, M. R. J. Lansdown, V. Speirs, and P. J. Carder Correspondence re: K. Heer et al., Serum Vascular Endothelial Growth Factor in Breast Cancer: Its Relation with Cancer Type and Estrogen Receptor Status. Clin. Cancer Res., 7: 3491-3494, 2001. Clin. Cancer Res., August 1, 2003; 9(9): 3514 - 3514. [Full Text] [PDF]
|
|
|
|
|
|
K. Heer Reply Clin. Cancer Res., August 1, 2003; 9(9): 3515 - 3515. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Dabrosin Variability of Vascular Endothelial Growth Factor in Normal Human Breast Tissue in Vivo during the Menstrual Cycle J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2695 - 2698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Danforth, L. K. Arbogast, S. Ghosh, A. Dickerman, R. Rofagha, and C. I. Friedman Vascular Endothelial Growth Factor Stimulates Preantral Follicle Growth in the Rat Ovary Biol Reprod, May 1, 2003; 68(5): 1736 - 1741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. J. J. Berns, J. G. M. Klijn, M. P. Look, N. Grebenchtchikov, R. Vossen, H. Peters, A. Geurts-Moespot, H. Portengen, I. L. van Staveren, M. E. Meijer-van Gelder, et al. Combined Vascular Endothelial Growth Factor and TP53 Status Predicts Poor Response to Tamoxifen Therapy in Estrogen Receptor-positive Advanced Breast Cancer Clin. Cancer Res., April 1, 2003; 9(4): 1253 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Stevens, J. Soden, P. E. Brenchley, S. Ralph, and D. W. Ray Haplotype Analysis of the Polymorphic Human Vascular Endothelial Growth Factor Gene Promoter Cancer Res., February 15, 2003; 63(4): 812 - 816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Buteau-Lozano, M. Ancelin, B. Lardeux, J. Milanini, and M. Perrot-Applanat Transcriptional Regulation of Vascular Endothelial Growth Factor by Estradiol and Tamoxifen in Breast Cancer Cells: A Complex Interplay between Estrogen Receptors {alpha} and {beta} Cancer Res., September 1, 2002; 62(17): 4977 - 4984. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Cracchiolo, J. W. Swick, L. McKiernan, E. Sloan, S. Raina, C. Sloan, and D. L. Wendell Estrogen-Dependent Growth of a Rat Pituitary Tumor Involves, But Does Not Require, a High Level of Vascular Endothelial Growth Factor Experimental Biology and Medicine, July 1, 2002; 227(7): 492 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Hyder The Role of Steroid Hormones on the Regulation of Vascular Endothelial Growth Factorm Am. J. Pathol., July 1, 2002; 161(1): 345 - 346. [Full Text] [PDF]
|
|
|
|
|
|
L. Bogin and H. Degani Hormonal Regulation of VEGF in Orthotopic MCF7 Human Breast Cancer Cancer Res., April 1, 2002; 62(7): 1948 - 1951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. N. TAYLOR, D. I. LEBOVIC, and M. D. MUELLER Angiogenic Factors in Endometriosis Ann. N.Y. Acad. Sci., March 1, 2002; 955(1): 89 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. TOSETTI, N. FERRARI, S. DE FLORA, and A. ALBINI Angioprevention': angiogenesis is a common and key target for cancer chemopreventive agents FASEB J, January 1, 2002; 16(1): 2 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Soares, J. S. Reis-Filho, F. Gartner, F. C. Schmitt, L. Iruela-Arispa, and M. D. Graubert Vascular Endothelial Growth Factor, Transforming Growth Factor-{alpha}, and Estrogen Receptors: Possible Cross-Talks and Interactions Am. J. Pathol., January 1, 2002; 160(1): 381 - 383. [Full Text] [PDF]
|
|
|
|
|
|
C. J. FABIAN and B. F. KIMLER Beyond Tamoxifen: New Endpoints for Breast Cancer Chemoprevention, New Drugs for Breast Cancer Prevention Ann. N.Y. Acad. Sci., December 1, 2001; 952(1): 44 - 59. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-J. Chew, X. Yuan, S. E. Scherer, L. Qie, F. Huang, W. P. Hayes, and V. Gallo Characterization of the Rat GRIK5 Kainate Receptor Subunit Gene Promoter and Its Intragenic Regions Involved in Neural Cell Specificity J. Biol. Chem., November 2, 2001; 276(45): 42162 - 42171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. N. TAYLOR, D. I. LEBOVIC, D. HORNUNG, and M. D. MUELLER Endocrine and Paracrine Regulation of Endometrial Angiogenesis Ann. N.Y. Acad. Sci., September 1, 2001; 943(1): 109 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Klinge Estrogen receptor interaction with estrogen response elements Nucleic Acids Res., July 15, 2001; 29(14): 2905 - 2919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Foekens, H. A. Peters, N. Grebenchtchikov, M. P. Look, M. E. Meijer-van Gelder, A. Geurts-Moespot, T. H. van der Kwast, C. G. J. Sweep, and J. G. M. Klijn High Tumor Levels of Vascular Endothelial Growth Factor Predict Poor Response to Systemic Therapy in Advanced Breast Cancer Cancer Res., July 1, 2001; 61(14): 5407 - 5414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Cardenas, K.A. Burke, R.M. Bigsby, W.F. Pope, and K.P. Nephew Estrogen Receptor {beta} in the Sheep Ovary During the Estrous Cycle and Early Pregnancy Biol Reprod, July 1, 2001; 65(1): 128 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Mills Changing colors in mice: an inducible system that delivers Genes & Dev., June 15, 2001; 15(12): 1461 - 1467. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Morii, H. Ogihara, K. Oboki, C. Sawa, T. Sakuma, S. Nomura, J. D. Esko, H. Handa, and Y. Kitamura Inhibitory effect of the mi transcription factor encoded by the mutant mi allele on GA binding protein-mediated transcript expression in mouse mast cells Blood, May 15, 2001; 97(10): 3032 - 3039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bos, H. Zhong, C. F. Hanrahan, E. C. M. Mommers, G. L. Semenza, H. M. Pinedo, M. D. Abeloff, J. W. Simons, P. J. van Diest, and E. van der Wall Levels of Hypoxia-Inducible Factor-1{{alpha}} During Breast Carcinogenesis J Natl Cancer Inst, February 21, 2001; 93(4): 309 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Blackwell, Z. A. Haroon, S. Shan, W. Saito, G. Broadwater, C. S. Greenberg, and M. W. Dewhirst Tamoxifen Inhibits Angiogenesis in Estrogen Receptor-negative Animal Models Clin. Cancer Res., November 1, 2000; 6(11): 4359 - 4364. [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 |
