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Regulation ofvascular endothelialgrowth factor (VEGF)gene transcription byestrogen receptors αand β Michael D. MuellerJean‐Louis VigneО. H. Minchenko2000 год

Regulation of vascular endothelial growth factor (VEGF) gene transcription by estrogen receptors α and β
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Аннотация: Vascular endothelial growth factor (VEGF) mediates angiogenic activity in a variety of estrogen target tissues. To determine whether estrogen has a direct transcriptional effect on VEGF gene expression, we developed a model system by transiently transfecting human VEGF promoter-luciferase reporter constructs into primary human endometrial cells and into Ishikawa cells, derived from a well-differentiated human endometrial adenocarcinoma. In primary endometrial epithelial cells, treatment with 17β-estradiol (E 2 ) resulted in a 3.8-fold increase in luciferase activity, whereas a 3.2-fold induction was demonstrated for stromal cells. Our Ishikawa cells had less than 100 functional estrogen receptors (ER)/cell and were therefore cotransfected with expression vectors encoding either the α- or the β-form of the human ER. In cells cotransfected with ERα, E 2 induced 3.2-fold induction in VEGF-promoter luciferase activity. A 2.3-fold increase was observed in cells cotransfected with ERβ. Through specific deletions, the E 2 response was restricted to a single 385-bp Pvu II- Sst I fragment in the 5′ flanking DNA. Cotransfection of this upstream region with a DNA binding domain ER mutant, or site-directed mutagenesis of a variant ERE within this fragment, resulted in the loss of the E 2 response. Electromobility shift assays demonstrated that this same ERE sequence specifically binds estradiol-ER complexes. These studies demonstrate that E 2 -regulated VEGF gene transcription requires a variant ERE located 1.5 kb upstream from the transcriptional start site. Site-directed mutagenesis of this ERE abrogated E 2 -induced VEGF gene expression.
Год издания: 2000
Авторы: Michael D. Mueller, Jean‐Louis Vigne, О. H. Minchenko, Dan I. Lebovic, Dale C. Leitman, Robert N. Taylor
Издательство: National Academy of Sciences
Источник: Proceedings of the National Academy of Sciences
Ключевые слова: Estrogen and related hormone effects, Angiogenesis and VEGF in Cancer, Inflammatory mediators and NSAID effects
Другие ссылки: Proceedings of the National Academy of Sciences (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)