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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2007-4-24
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pubmed:abstractText |
We have previously demonstrated that spontaneous DNA synthesis in immature thymocytes of Atm-/- mice is elevated, and that treatment with the glucocorticoid dexamethasone (Dex) attenuates this increased DNA synthesis and prevents the development of thymic lymphomas. Deregulation of c-myc may drive the uncontrolled proliferation of Atm-/- thymocytes, since upregulation of c-myc parallels the elevated DNA synthesis in the cells. In this study, we show that the glucocorticoid receptor (GR) is expressed at high levels in Atm-/- thymocytes and in Atm-/- thymic lymphoma cells, although serum glucocorticoid (GC) levels in Atm-/- mice are similar to those in Atm+/+ mice. In cultured Atm-/- thymic lymphoma cells treated with Dex, GR nuclear translocation occurs, resulting in suppression of DNA synthesis and c-myc expression at both the mRNA and protein levels. Interestingly, the GR antagonist RU486 also causes GR nuclear translocation, but does not affect DNA synthesis and c-myc expression in Atm-/- thymic lymphoma cells. As expected, RU486 reverses the suppressive effects of Dex on DNA synthesis and c-myc expression. Administration of Dex to Atm-/- mice decreases the elevated c-Myc protein levels in their thymocytes. These findings suggest that GC/GR signaling plays an important role in regulating c-myc expression in Atm-/- thymocytes and thymic lymphoma cells.
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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/Antineoplastic Agents, Hormonal,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Hormone Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Mifepristone,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucocorticoid,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ataxia telangiectasia mutated...
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0039-128X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
72
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
415-21
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:17418878-Active Transport, Cell Nucleus,
pubmed-meshheading:17418878-Animals,
pubmed-meshheading:17418878-Antineoplastic Agents, Hormonal,
pubmed-meshheading:17418878-Cell Cycle Proteins,
pubmed-meshheading:17418878-Cell Line, Tumor,
pubmed-meshheading:17418878-Cell Nucleus,
pubmed-meshheading:17418878-DNA,
pubmed-meshheading:17418878-DNA-Binding Proteins,
pubmed-meshheading:17418878-Dexamethasone,
pubmed-meshheading:17418878-Gene Expression Regulation, Leukemic,
pubmed-meshheading:17418878-Hormone Antagonists,
pubmed-meshheading:17418878-Lymphoma,
pubmed-meshheading:17418878-Mice,
pubmed-meshheading:17418878-Mice, Knockout,
pubmed-meshheading:17418878-Mifepristone,
pubmed-meshheading:17418878-Protein-Serine-Threonine Kinases,
pubmed-meshheading:17418878-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:17418878-Receptors, Glucocorticoid,
pubmed-meshheading:17418878-Signal Transduction,
pubmed-meshheading:17418878-Thymus Gland,
pubmed-meshheading:17418878-Tumor Suppressor Proteins
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pubmed:year |
2007
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pubmed:articleTitle |
The glucocorticoid receptor is increased in Atm-/- thymocytes and in Atm-/- thymic lymphoma cells, and its nuclear translocation counteracts c-myc expression.
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pubmed:affiliation |
The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, 1808 Park Road 1C, Smithville, TX 78957, USA. mingyan@mdanderson.org
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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