| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 17, 2003
Accepted on June 3, 2004
IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, 4200 Porto, Portugal; Breast Cancer Research Lab, Fox Chase Cancer Center, Philadelphia, 19111PA, USA; Medical Faculty, University of Porto, 4200 Porto, Portugal; Molecular Pathology Unit, Portuguese Institute of Oncology - 4200 Porto, Portugal; Pathology Dept., ICBAS- Instituto de Ciências Biomédicas Abel Salazar, 4050 Porto, Portugal
* To whom correspondence should be addressed. E-mail: raquel.soares{at}ipatimup.pt.
We have investigated the molecular mechanisms involved in 17
-estradiol-induced angiogenic pathway. We show here that 17-estradiol promoted a six-fold increase in Jagged1 expression and an eight-fold increase in Notch1 expression by cDNA arrays in breast cancer MCF7 cells. Interestingly, Jagged1 was abrogated by incubation with the estrogen antagonist, ICI182,780. A similar up-regulation of both Notch1 receptor and Jagged1 ligand was found in endothelial cells. Additionally, imperfect estrogen responsive elements were found in the 5' untranslated region of Notch1 and Jagged1 genes. Treatment with 17-estradiol also led to an activation of Notch signaling in MCF7 cells expressing Notch1 reporter gene or by promoting Jagged1-induced Notch signaling in coculture assays. Inoculation of MCF7 cells in 17-estradiol-treated nude mice resulted in up-regulation of Notch1 expression as well as increased number of tumor microvessels in comparison to placebo-treated mice. Notch1-expressing endothelial cell cultures formed cord-like structures on Matrigel in contrast to cells expressing a dominant negative form of Notch1, emphasizing the relevance of Notch1 pathway in vessel assembly. Finally, Notch1-expressing MCF7 cells up-regulated HIF1
gene, a well-known angiogenic factor that clustered with Notch1 gene. This study implicates Notch signaling in the cross talk between 17-estradiol and angiogenesis.
•
tumor vessels
NURSA Molecule Pages Link:
This article has been cited by other articles:
 |
|
 |
|
  P. Rizzo, H. Miao, G. D'Souza, C. Osipo, J. Yun, H. Zhao, J. Mascarenhas, D. Wyatt, G. Antico, L. Hao, et al. Cross-talk between Notch and the Estrogen Receptor in Breast Cancer Suggests Novel Therapeutic Approaches Cancer Res., July 1, 2008; 68(13): 5226 - 5235. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. F. O'Neill, S. Urs, C. Cinelli, A. Lincoln, R. J. Nadeau, R. Leon, J. Toher, C. Mouta-Bellum, R. E. Friesel, and L. Liaw Notch2 Signaling Induces Apoptosis and Inhibits Human MDA-MB-231 Xenograft Growth Am. J. Pathol., September 1, 2007; 171(3): 1023 - 1036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Rodrigues, J. A. Teixeira, F. L. Schmitt, M. Paulsson, and H. Lindmark-Mansson The Role of Osteopontin in Tumor Progression and Metastasis in Breast Cancer Cancer Epidemiol. Biomarkers Prev., June 1, 2007; 16(6): 1087 - 1097. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Zoller and G. J. Kersh Estrogen Induces Thymic Atrophy by Eliminating Early Thymic Progenitors and Inhibiting Proliferation of beta-Selected Thymocytes. J. Immunol., June 15, 2006; 176(12): 7371 - 7378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. G. Leong and A. Karsan Recent insights into the role of Notch signaling in tumorigenesis Blood, March 15, 2006; 107(6): 2223 - 2233. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
