ArticleMolecular endocrinology (Baltimore, Md.)2008
Vascular endothelial growth factor receptor-2 expression is down-regulated by 17beta-estradiol in MCF-7 breast cancer cells by estrogen receptor alpha/Sp proteins.
Article in Molecular endocrinology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Activation of Genes by Nuclear Receptor/Specificity Protein (Sp) Interactions in Cancer.Cancers · 2025Review
- VEGFR-Mediated Cytotoxic Activity ofLife (Basel, Switzerland) · 2021Article
- Article
- The Multifaceted Nature of Tumor Microenvironment in Breast Carcinomas.Pathobiology : journal of immunopathology, molecular and cellular biology · 2020Review
- Proximal and distal regulation of the HYAL1 gene cluster by the estrogen receptor α in breast cancer cells.Oncotarget · 2016Article
- Influence of VEGFR and LHCGR on endometrial adenocarcinoma.Oncology letters · 2016Article
- The complex nature of oestrogen signalling in breast cancer: enemy or ally?Bioscience reports · 2016Review
- 17β-Estradiol Ameliorates Tight Junction Disruption via Repression of MMP Transcription.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Up-regulation of type II collagen gene by 17β-estradiol in articular chondrocytes involves Sp1/3, Sox-9, and estrogen receptor α.Journal of molecular medicine (Berlin, Germany) · 2014Article
- Significance of estrogen receptor subtypes in breast tumorigenesis and progression.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Vascular endothelial growth factor receptor-2 in breast cancer.Biochimica et biophysica acta · 2010Review
- Article
- MicroRNA cluster 221-222 and estrogen receptor alpha interactions in breast cancer.Journal of the National Cancer Institute · 2010Article
- Down-regulation of PROS1 gene expression by 17beta-estradiol via estrogen receptor alpha (ERalpha)-Sp1 interaction recruiting receptor-interacting protein 140 and the corepressor-HDAC3 complex.The Journal of biological chemistry · 2010Article
- Angiogenesis and breast cancer.Journal of oncology · 2010Article
- Histone deacetylase 7 and FoxA1 in estrogen-mediated repression of RPRM.Molecular and cellular biology · 2010Article
- Repression of ESR1 through actions of estrogen receptor alpha and Sin3A at the proximal promoter.Molecular and cellular biology · 2009Article
- Estradiol downregulation of the tumor suppressor gene BTG2 requires estrogen receptor-alpha and the REA corepressor.International journal of cancer · 2009Article
- Impact of vascular endothelial growth factor receptor 1, 2, and 3 expression on the outcome of patients with gastric cancer.Cancer science · 2009Article
- Role of SP transcription factors in hormone-dependent modulation of genes in MCF-7 breast cancer cells: microarray and RNA interference studies.Journal of molecular endocrinology · 2009Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
17beta-Estradiol (E2) induces and represses gene expression in breast cancer cells; however, the mechanisms of gene repression are not well understood. In this study, we show that E2 decreases vascular endothelial growth factor receptor 2 (VEGFR2) mRNA levels in MCF-7 cells, and this gene was used as a model for investigating pathways associated with E2-dependent gene repression. Deletion analysis of the VEGFR2 promoter indicates that the proximal GC-rich motifs at -58 and -44 are critical for the E2-dependent decreased response in MCF-7 cells. Mutation or deletion of these GC-rich elements results in loss of hormone responsiveness and shows that the -60 to -37 region of the VEGFR2 promoter is critical for both basal and hormone-dependent decreased VEGFR2 expression in MCF-7 cells. Western blot, immunofluorescent staining, RNA interference, and EMSAs support a role for Sp proteins in hormone-dependent down-regulation of VEGFR2 in MCF-7 cells, primarily through estrogen receptor (ER)alpha/Sp1 and ERalpha/Sp3 interactions with the VEGFR2 promoter. Using chromatin immuno-precipitation and transient transfection/RNA interference assays we show that the ERalpha/Sp protein-promoter interactions are accompanied by recruitment of the co-repressors SMRT (silencing mediator of retinoid and thyroid hormone receptor) and NCoR (nuclear receptor corepressor) to the promoter and that SMRT and NCoR knockdown reverse E2-mediated down-regulation of VEGFR2 expression in MCF-7 cells. This study illustrates that both SMRT and NCoR are involved in E2-dependent repression of VEGFR2 in MCF-7 cells.
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