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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
20
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pubmed:dateCreated |
2000-11-3
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pubmed:abstractText |
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 17beta-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 alpha- or the beta-form of the human ER. In cells cotransfected with ERalpha, E(2) induced 3.2-fold induction in VEGF-promoter luciferase activity. A 2.3-fold increase was observed in cells cotransfected with ERbeta. Through specific deletions, the E(2) response was restricted to a single 385-bp PvuII-SstI 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.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-10027602,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-10199791,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-10381820,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-10445820,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-10446899,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-10466115,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-10469350,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-10503719,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-10599737,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-13698100,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-1373641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-1545816,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-1569962,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-1711045,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-1791831,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-2476951,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-2792078,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-2916436,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-3167974,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-3340549,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-3458212,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-3690665,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-3754034,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-434029,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-7523199,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-7525061,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-7528597,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-7659088,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-8078914,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-8126136,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-8288707,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-8344219,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-8466753,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-8481475,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-8608615,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-8756718,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-8768883,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-8843410,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-8885054,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-9202240,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-9291439,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-9500609,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-9814484,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10995484-9893343
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
97
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10972-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10995484-Cells, Cultured,
pubmed-meshheading:10995484-Endometrium,
pubmed-meshheading:10995484-Endothelial Growth Factors,
pubmed-meshheading:10995484-Estrogen Receptor alpha,
pubmed-meshheading:10995484-Estrogen Receptor beta,
pubmed-meshheading:10995484-Female,
pubmed-meshheading:10995484-Gene Transfer Techniques,
pubmed-meshheading:10995484-Humans,
pubmed-meshheading:10995484-Lymphokines,
pubmed-meshheading:10995484-Receptors, Estrogen,
pubmed-meshheading:10995484-Sequence Deletion,
pubmed-meshheading:10995484-Transcription, Genetic,
pubmed-meshheading:10995484-Transcriptional Activation,
pubmed-meshheading:10995484-Vascular Endothelial Growth Factor A,
pubmed-meshheading:10995484-Vascular Endothelial Growth Factors
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pubmed:year |
2000
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pubmed:articleTitle |
Regulation of vascular endothelial growth factor (VEGF) gene transcription by estrogen receptors alpha and beta.
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pubmed:affiliation |
Center for Reproductive Sciences, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA 94143-0556, USA.
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pubmed:publicationType |
Journal Article
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