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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0040648,
umls-concept:C0079904,
umls-concept:C0086661,
umls-concept:C0086982,
umls-concept:C0185117,
umls-concept:C0334227,
umls-concept:C0346647,
umls-concept:C0678226,
umls-concept:C1521840,
umls-concept:C1879547,
umls-concept:C2911684
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pubmed:issue |
53
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pubmed:dateCreated |
2004-11-11
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pubmed:abstractText |
The persistent activation of signaling cascades results in dramatic consequences that include loss of cellular growth control and neoplastic transformation. We show here that phosphoinositide 3-kinase (PI 3-kinase) and its mediator Akt were constitutively activated in pancreatic cancer and that this might be due to the aberrant expression of their natural antagonist MMAC/PTEN. Indeed, our results show that MMAC/PTEN expression was either lost or significantly reduced in five of eight cell lines and in twelve of seventeen tumor specimens examined. That the poor expression of MMAC/PTEN in pancreatic cancer cells could be due to promoter methylation was indicated by methylation-specific PCR analysis. Our studies also indicated that PI 3-kinase targeted two important transcription factors in pancreatic cancer cells. The ability of constitutively activated NF-kappaB to induce gene expression and the stabilization of c-MYC protein by decreased phosphorylation of Thr58 were both dependent on PI 3-kinase activity. When pancreatic cancer cells were treated with a peptide antagonist of NF-kappaB nuclear translocation, or stably transfected with a dominant-negative mutant of MYC, their proliferation was markedly inhibited. Taken together, these data indicate that the aberrant expression of MMAC/PTEN contributes to the activation of the PI 3-kinase/Akt pathway and its transcription factor mediators in pancreatic cancer.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN Phosphohydrolase,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases,
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-myc,
http://linkedlifedata.com/resource/pubmed/chemical/Threonine,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8571-80
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15467756-Cell Line, Tumor,
pubmed-meshheading:15467756-Cell Proliferation,
pubmed-meshheading:15467756-Humans,
pubmed-meshheading:15467756-NF-kappa B,
pubmed-meshheading:15467756-PTEN Phosphohydrolase,
pubmed-meshheading:15467756-Pancreatic Neoplasms,
pubmed-meshheading:15467756-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:15467756-Phosphoric Monoester Hydrolases,
pubmed-meshheading:15467756-Phosphorylation,
pubmed-meshheading:15467756-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15467756-Proto-Oncogene Proteins,
pubmed-meshheading:15467756-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15467756-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:15467756-Signal Transduction,
pubmed-meshheading:15467756-Threonine,
pubmed-meshheading:15467756-Tumor Suppressor Proteins
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pubmed:year |
2004
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pubmed:articleTitle |
The PI 3-kinase/Akt signaling pathway is activated due to aberrant Pten expression and targets transcription factors NF-kappaB and c-Myc in pancreatic cancer cells.
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pubmed:affiliation |
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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