Evidence for the Notch signaling pathway on the role of estrogen in angiogenesis

• Type: Article in International Scientific Journal
• Date: 2004

Authors

soares, r (Author) FMUP; balogh, g (Author) Other; guo, s (Author) Other; gartner, f (Author) ICBAS; russo, j (Author) Other; schmitt, f (Author) FMUP

Journal

Title: Molecular Endocrinology

Vol. 18

Pages: 2333-2343

ISSN: 0888-8809

Publisher: The Endocrine Society

Indexing

ISI Web of Knowledge - 112 Citations

Scopus - 128 Citations

Other information

Authenticus ID: P-000-8VH

DOI: 10.1210/me.2003-0362

Abstract (EN): We have investigated the molecular mechanisms involved in 17beta-estradiol-induced angiogenic pathway. We show here that 17beta-estradiol promoted a 6-fold increase in Jagged1 expression and an 8-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 upregulation 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 17beta-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 17beta-estradiol-treated nude mice resulted in upregulation 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 upregulated hypoxia-inducible factor 1alpha gene, a well-known angiogenic factor that clustered with Notch1 gene. This study implicates Notch signaling in the cross talk between 17beta-estradiol and angiogenesis.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11