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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
2004-10-6
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pubmed:abstractText |
Following DNA damage, human cells arrest primarily in the G(1) and G(2) phases of the cell cycle. Here, we show that after irradiation, human cancer cells with targeted deletion of PTEN or naturally occurring PTEN mutations can exert G(1) and G(2) arrests but are unable to arrest in size. Pharmacological inhibition of phosphoinositol-3-kinase or mTOR in PTEN(-/-) cells restored the size arrest, whereas siRNA-mediated depletion of TSC2 in PTEN(+/+) cells attenuated the size arrest. Radiation treatment potentiated Akt activation in PTEN(-/-) but not PTEN(+/+) cells. Finally, abrogation of the size arrest via PTEN deletion conferred radiosensitivity both in vitro and in vivo. These results identify a new tumor suppressor gene-regulated, DNA damage-inducible arrest that occurs simultaneously with the G(1) and G(2) arrests but is genetically separable from them. We suggest that aberrant regulation of cell size during cell cycle arrest may be important in human cancer pathogenesis.
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pubmed:grant |
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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/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/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/tuberous sclerosis complex 2 protein
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
64
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6906-14
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pubmed:dateRevised |
2011-9-22
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pubmed:meshHeading |
pubmed-meshheading:15466180-Animals,
pubmed-meshheading:15466180-Cell Division,
pubmed-meshheading:15466180-Cell Line, Tumor,
pubmed-meshheading:15466180-DNA Damage,
pubmed-meshheading:15466180-Enzyme Activation,
pubmed-meshheading:15466180-G1 Phase,
pubmed-meshheading:15466180-G2 Phase,
pubmed-meshheading:15466180-Humans,
pubmed-meshheading:15466180-Mice,
pubmed-meshheading:15466180-Neoplasm Transplantation,
pubmed-meshheading:15466180-Neoplasms,
pubmed-meshheading:15466180-PTEN Phosphohydrolase,
pubmed-meshheading:15466180-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:15466180-Phosphoric Monoester Hydrolases,
pubmed-meshheading:15466180-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15466180-Proto-Oncogene Proteins,
pubmed-meshheading:15466180-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15466180-RNA, Small Interfering,
pubmed-meshheading:15466180-Radiation Tolerance,
pubmed-meshheading:15466180-Repressor Proteins,
pubmed-meshheading:15466180-Signal Transduction,
pubmed-meshheading:15466180-Transplantation, Heterologous,
pubmed-meshheading:15466180-Tumor Suppressor Proteins
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pubmed:year |
2004
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pubmed:articleTitle |
PTEN gene targeting reveals a radiation-induced size checkpoint in human cancer cells.
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pubmed:affiliation |
Department of Oncology and Tumor Biology Training Program, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, District of Columbia 20057, 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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