Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2005-8-16
pubmed:abstractText
Hepatocyte growth factor/scatter factor (HGF) and the angiogenesis factors platelet-derived growth factors (PDGF), vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) are found in elevated concentrations in serum or tumor tissue of patients with head and neck squamous cell carcinomas (HNSCC), suggesting these factors may be coregulated. A cDNA microarray analysis for HGF-inducible genes revealed that HGF also modulates PDGFA expression, a gene recently shown to be inducible by the transcription factor, early growth response-1 (Egr-1). In the present study, we investigated the potential role of HGF-induced Egr-1 in expression of PDGF, VEGF, and IL-8. HGF induced expression of all three factors and Egr-1 expression and DNA-binding activity. The analysis of promoter sequences showed putative Egr-1 binding sites in the PDGFA or VEGF but not in the IL-8 promoter, and HGF-induced Egr-1-binding activity was confirmed by chromatin immunoprecipitation (ChIP) assay. The maximal basal and HGF-induced promoter activity for the PDGFA gene existed within -630 bp of the promoter region, and overexpression of Egr-1 significantly increased such activity. Consistent with this, expression of PDGFA and VEGF but not IL-8 showed corresponding differences with Egr-1 expression in HNSCC tumor specimens and were strongly suppressed by transfection of Egr-1-antisense or small interference RNA (siRNA) oligonucleotides. HGF-induced expression of Egr-1, PDGFA, and VEGF was suppressed by pharmacologic and siRNA inhibitors of mitogen-activated protein kinase kinase 1/2 (MEK1/2) and protein kinase C (PKC) pathways. We conclude that the HGF-induced activation of transcription factor Egr-1 by MEK1/2- and PKC-dependent mechanisms differentially contributes to expression of PDGF and VEGF, which are important angiogenesis factors and targets for HNSCC therapy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Angiogenic Proteins, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/EGR1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Early Growth Response Protein 1, http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8, http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 2, http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A, http://linkedlifedata.com/resource/pubmed/chemical/platelet-derived growth factor A
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7071-80
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16103054-Angiogenic Proteins, pubmed-meshheading:16103054-Base Sequence, pubmed-meshheading:16103054-Carcinoma, Squamous Cell, pubmed-meshheading:16103054-Cell Line, Tumor, pubmed-meshheading:16103054-DNA-Binding Proteins, pubmed-meshheading:16103054-Early Growth Response Protein 1, pubmed-meshheading:16103054-Gene Expression Regulation, Neoplastic, pubmed-meshheading:16103054-Head and Neck Neoplasms, pubmed-meshheading:16103054-Hepatocyte Growth Factor, pubmed-meshheading:16103054-Humans, pubmed-meshheading:16103054-Immediate-Early Proteins, pubmed-meshheading:16103054-Interleukin-8, pubmed-meshheading:16103054-MAP Kinase Kinase 1, pubmed-meshheading:16103054-MAP Kinase Kinase 2, pubmed-meshheading:16103054-Microdissection, pubmed-meshheading:16103054-Molecular Sequence Data, pubmed-meshheading:16103054-Oligonucleotides, Antisense, pubmed-meshheading:16103054-Phosphatidylinositol 3-Kinases, pubmed-meshheading:16103054-Platelet-Derived Growth Factor, pubmed-meshheading:16103054-Protein Kinase C, pubmed-meshheading:16103054-RNA, Small Interfering, pubmed-meshheading:16103054-Transcription Factors, pubmed-meshheading:16103054-Transfection, pubmed-meshheading:16103054-Vascular Endothelial Growth Factor A
pubmed:year
2005
pubmed:articleTitle
Hepatocyte growth factor/scatter factor differentially regulates expression of proangiogenic factors through Egr-1 in head and neck squamous cell carcinoma.
pubmed:affiliation
Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland 20892-1419, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural