|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0031621,
umls-concept:C0037083,
umls-concept:C0078058,
umls-concept:C0127400,
umls-concept:C0162493,
umls-concept:C0812222,
umls-concept:C0871261,
umls-concept:C1171892,
umls-concept:C1521761,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C1710082,
umls-concept:C2911692
|
|
pubmed:issue |
44
|
|
pubmed:dateCreated |
2004-10-25
|
|
pubmed:abstractText |
Vascular endothelial growth factor (VEGF) expression is elevated in ovarian and other cancer cells. However, the mechanism that causes the increase in VEGF expression still remains to be elucidated. In this study, we demonstrated that activation of PI3K signaling mediated VEGF protein expression at the transcriptional level through hypoxia-inducible factor 1alpha (HIF-1alpha) expression in human ovarian cancer cells. We found that inhibition of PI3K activity by LY294002 decreased VEGF transcriptional activation and that forced expression of AKT completely reversed the inhibitory effect. HDM2 and p70S6K1 are two downstream targets of AKT that mediate growth factor-induced VEGF transcriptional activation and HIF-1alpha expression. The inhibition of PI3K by LY294002 inhibited p70S6K1 and HDM2 activity in the cells. Forced expression of p70S6K1 or HDM2 reversed LY294002-inhibited VEGF transcriptional activation and HIF-1alpha expression. This study identifies a potential novel mechanism responsible for increased VEGF expression in ovarian cancer cells. It also indicates the important role of VEGF and HIF-1 in ovarian tumorigenesis and angiogenesis, which is mediated by the PI3K/AKT/HDM2 and AKT/p70S6K1 pathways in ovarian cancer cells.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/MDM2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-mdm2,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases, 70-kDa,
http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Oct
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
29
|
|
pubmed:volume |
279
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
45643-51
|
|
pubmed:dateRevised |
2010-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:15337760-Cell Line, Tumor,
pubmed-meshheading:15337760-Chromones,
pubmed-meshheading:15337760-DNA-Binding Proteins,
pubmed-meshheading:15337760-Female,
pubmed-meshheading:15337760-Humans,
pubmed-meshheading:15337760-Hypoxia-Inducible Factor 1,
pubmed-meshheading:15337760-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:15337760-Morpholines,
pubmed-meshheading:15337760-Nuclear Proteins,
pubmed-meshheading:15337760-Ovarian Neoplasms,
pubmed-meshheading:15337760-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:15337760-Phosphorylation,
pubmed-meshheading:15337760-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15337760-Proto-Oncogene Proteins,
pubmed-meshheading:15337760-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15337760-Proto-Oncogene Proteins c-mdm2,
pubmed-meshheading:15337760-Ribosomal Protein S6 Kinases, 70-kDa,
pubmed-meshheading:15337760-Signal Transduction,
pubmed-meshheading:15337760-Sirolimus,
pubmed-meshheading:15337760-Transcription Factors,
pubmed-meshheading:15337760-Transcriptional Activation,
pubmed-meshheading:15337760-Vascular Endothelial Growth Factor A
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
Vascular endothelial growth factor transcriptional activation is mediated by hypoxia-inducible factor 1alpha, HDM2, and p70S6K1 in response to phosphatidylinositol 3-kinase/AKT signaling.
|
|
pubmed:affiliation |
Mary Babb Randolph Cancer Center, Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, West Virginia 26506-9300, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
