| Central role of p53 on regulation of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) expression in mammary carcinoma. | |
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MedLine Citation:
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PMID: 11559575 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The process of angiogenic switching is one of the most important factors in the growth and development of breast tumors. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is considered to be the most important directly acting angiogenic protein that has been shown to be up-regulated in breast cancer cells. Hypoxia seems to be an important stimulus for inducing VPF/VEGF mRNA expression in human mammary tumors. Here, we have studied the roles of the tumor suppressor gene p53 and the proto-oncogene c-Src in regulating the transcription of VPF/VEGF in breast cancer cell lines MCF-7 and MDA-MB 435 under both normoxic and hypoxic conditions. p53 significantly inhibited the transcription of VPF/VEGF involving the transcription factor Sp1. Increased binding of Sp1 to the VPF/VEGF promoter has been observed when the cells were exposed to hypoxia. It has been shown that p53 makes a complex with Sp1 and inhibits its binding to the VPF/VEGF promoter to prevent the transcriptional activation. Furthermore, c-Src kinase activity was found to be increased in the hypoxic condition, and in the presence of antisense of Src, there was down-regulation of the total mRNA level and also the promoter activity of VPF/VEGF. The present study indicates that p53 can also inhibit the hypoxic induction of Src kinase activity and thereby may prevent VPF/VEGF transcription. Taken together, our data suggest a central role of p53, through which it can inhibit VPF/VEGF expression by regulating the transcriptional activity of Sp1 and also by down-regulating the Src kinase activity, under both normoxic and hypoxic conditions. |
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Authors:
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S Pal; K Datta; D Mukhopadhyay |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cancer research Volume: 61 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 2001 Sep |
Date Detail:
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Created Date: 2001-09-17 Completed Date: 2001-10-11 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 6952-7 Citation Subset: IM |
Affiliation:
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Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Breast Neoplasms
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enzymology,
genetics,
metabolism* Cell Hypoxia / physiology Down-Regulation / physiology Endothelial Growth Factors / biosynthesis*, genetics Enzyme Activation Gene Expression Regulation, Neoplastic / physiology* Genes, p53 / physiology* Humans Lymphokines / biosynthesis*, genetics Promoter Regions, Genetic RNA, Messenger / biosynthesis, genetics Sp1 Transcription Factor / antagonists & inhibitors, metabolism, physiology Transcriptional Activation / physiology Tumor Cells, Cultured Tumor Suppressor Protein p53 / metabolism, physiology* Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors src-Family Kinases / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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CA78383/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Endothelial Growth Factors; 0/Lymphokines; 0/RNA, Messenger; 0/Sp1 Transcription Factor; 0/Tumor Suppressor Protein p53; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors; EC 2.7.10.2/src-Family Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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