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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2009-1-13
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pubmed:abstractText |
Adenocarcinomas of the lung commonly show an increase in the activity of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, yet many are resistant to apoptosis induced by the inhibition of PI3K. We hypothesized that Bcl-xL would have a synergistic effect on the apoptotic response induced by inhibition of the PI3K/Akt pathway in lung adenocarcinoma. To test this, we examined the effect of the PI3K inhibitor (LY294002) on lung adenocarcinoma cell lines expressing varying levels of Bcl-xL. We found that cells that overexpress Bcl-xL are resistant to LY294002-induced apoptosis, whereas cells that express little Bcl-xL readily are not. Restoring Bcl-xL expression in cells that express low level of Bcl-xL conferred resistance to apoptosis in response to LY294002. The simultaneous inhibition of the PI3K/Akt pathway by LY294002 or Akt1 small interfering RNA and Bcl-xL function by ABT-737 or Bcl-xL small interfering RNA greatly enhanced the apoptotic response. Moreover, this response was associated with the induction of proapoptotic BH3-only Bcl-2 family member Bim. Our data suggest that PI3K/Akt and Bcl-xL pathways control cell death in lung adenocarcinoma cells in a synergistic manner. Modulation of Bcl-xL expression may represent one important strategy to optimize the efficacy of therapeutic agents targeting the PI3K/Akt pathway in adenocarcinoma of the lung.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19139118-10595916,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19139118-10777620,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19139118-10938285,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19139118-9529605
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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/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Bcl-2-like protein 11,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
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/bcl-X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1535-7163
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
101-9
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pubmed:dateRevised |
2011-7-28
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pubmed:meshHeading |
pubmed-meshheading:19139118-Adenocarcinoma,
pubmed-meshheading:19139118-Apoptosis,
pubmed-meshheading:19139118-Apoptosis Regulatory Proteins,
pubmed-meshheading:19139118-Cell Line, Tumor,
pubmed-meshheading:19139118-Chromones,
pubmed-meshheading:19139118-Humans,
pubmed-meshheading:19139118-Lung Neoplasms,
pubmed-meshheading:19139118-Membrane Proteins,
pubmed-meshheading:19139118-Morpholines,
pubmed-meshheading:19139118-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:19139118-Protein Kinase Inhibitors,
pubmed-meshheading:19139118-Proto-Oncogene Proteins,
pubmed-meshheading:19139118-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:19139118-Signal Transduction,
pubmed-meshheading:19139118-Substrate Specificity,
pubmed-meshheading:19139118-bcl-X Protein
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pubmed:year |
2009
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pubmed:articleTitle |
Synergy between phosphatidylinositol 3-kinase/Akt pathway and Bcl-xL in the control of apoptosis in adenocarcinoma cells of the lung.
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