Linked Life Data

17169602

Source:http://linkedlifedata.com/resource/pubmed/id/17169602

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2007-8-21
pubmed:abstractText
Overexpression of vascular endothelial growth factor (VEGF) is associated with angiogenic phenotypes and poor prognosis of numerous tumors, including head and neck squamous cell carcinoma (HNSCC). However, the precise mechanism that causes VEGF overexpression in HNSCC remains unknown. Since there is evidence that a transcriptional factor, signal transducers and activators of transcription 3 (Stat3), is constitutively activated in HNSCC and this activation is significantly associated with aggressive phenotypes of this disease, we investigated the roles of Stat3 activation on VEGF production and tumor angiogenesis in HNSCC both in vitro and in clinical samples. VEGF promoter assays with YCU-H891 cells demonstrated that dominant negative Stat3 significantly inhibited VEGF promoter activity in the full length (-2279 to +54) and two truncated forms of VEGF promoter luciferase-reporter construct (-1179 to 54) or (-1014 to +54), which retain the putative Stat3 responsive elements (-849 to -842). However, this was not seen in the shorter construct (-794 to +54), which lacks the putative Stat3 responsive elements. In the derivative of YCU-891 cells that stably express dominant negative Stat3 protein, cellular levels of VEGF mRNA and VEGF protein were significantly inhibited. In the 51 clinical samples obtained from the patients with tongue carcinoma, the expression levels of phosphorylated (activated) form of Stat3 protein were significantly correlated with VEGF (P<0.05) production and intratumoral microvessel density IMVD (P<0.01). These results strongly indicate that Stat3 directly up-regulates VEGF transcription and thereby promotes angiogenesis in HNSCC. Inhibition of Stat3 activity may provide a new anti-angiogenic therapy in HNSCC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1368-8375
pubmed:author
pubmed:issnType
Print
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
785-90
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Signal transducers and activators of transcription 3 up-regulates vascular endothelial growth factor production and tumor angiogenesis in head and neck squamous cell carcinoma.
pubmed:affiliation
Department of Otorhinolaryngology, Kyushu Koseinenkin Hospital, 2-1-1, Kishinoura, Nishiku, Kitakyushu 806-8501, Japan. muneyuki.masuda@qkn-hosp.jp
pubmed:publicationType
Journal Article