| Suppression of PI3K/mTOR pathway rescues LLC cells from cell death induced by hypoxia. | |
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MedLine Citation:
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PMID: 15781267 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cancer cells in solid tumors are challenged by various microenvironmental stresses, including hypoxia, and cancer cells in hypoxic regions are resistant to current cancer therapies. To investigate the mechanism of resistance to hypoxia in cancer cells, we examined mouse Lewis lung carcinoma (LLC) cells, which died due to necrosis at high density under hypoxic but not under normoxic conditions. Levels of mammalian target of rapamycin (mTOR), a central regulator of cellular energy, are reported to be suppressed in hypoxia. We found that phosphorylation of two molecules downstream to it, ribosomal p70 S6 kinase (S6K) and ribosomal protein S6, was markedly suppressed by hypoxia. Overexpression of the active form of S6K increased the sensitivity of LLC cells to hypoxia. On the other hand, inhibition of PI3K or mTOR dramatically reduced hypoxia-induced cell death under hypoxic conditions. Under hypoxic conditions, blockade of the PI3K or mTOR pathway increased levels of intracellular ATP and delayed decreases in pH and glucose level in culture medium, without affecting the cell cycle. |
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Authors:
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Y Hamanaka; M Mukai; M Shimamura; T Kitagawa; T Nishida; F Isohashi; T Ito; Y Nishizawa; M Tatsuta; H Matsuda; M Inoue |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 330 ISSN: 0006-291X ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2005 Apr |
Date Detail:
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Created Date: 2005-03-22 Completed Date: 2005-05-26 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 318-26 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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metabolism* Adenosine Triphosphate / metabolism Animals Carcinoma, Lewis Lung / enzymology, metabolism, pathology* Cell Death* Cell Hypoxia* Culture Media Glucose / metabolism Hydrogen-Ion Concentration Mice Necrosis Phosphorylation Protein Kinases / metabolism* Ribosomal Protein S6 Kinases / metabolism Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Culture Media; 50-99-7/Glucose; 56-65-5/Adenosine Triphosphate; EC 2.7.-/Protein Kinases; EC 2.7.1.-/mTOR protein; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Ribosomal Protein S6 Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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