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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 |
2010-5-31
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pubmed:abstractText |
2-Chloro-10-[3(-dimethylamino)propyl]phenothiazinemonohydrochloride (chlorpromazine) is a phenothiazine derivative used clinically to control psychotic disorders. It also exhibits an anticancer activity. Treatment with chlorpromazine (CPZ) results in cell-cycle arrest at the G2/M phase in rat C6 glioma cells. CPZ reduces the expression of cell cycle-related proteins, such as cyclin D1, cyclin A, and cyclin B1, but causes an increase in the p21(Waf1/Cip1) level. The molecular mechanism by which CPZ regulates p21(Waf1/Cip1) expression is unknown. Here, we provide evidence that CPZ activates the p21(Waf1/Cip1) gene promoter via induction of the transcription factor early growth response-1 (Egr-1) independently of p53 in C6 cells. A point mutation in the Egr-1-binding motif within the p21(Waf1/Cip1) promoter abrogated promoter inducibility due to CPZ. Forced expression of Egr-1 enhanced p21(Waf1/Cip1) promoter activity. In contrast, knockdown of endogenous Egr-1 by small interference RNA attenuated CPZ-induced p21(Waf1/Cip1) promoter activity. A chromatin immunoprecipitation assay demonstrated that Egr-1 binds to the p21(Waf1/Cip1) gene promoter. Further analysis showed that the ERK and JNK MAP kinases are required for induction of Egr-1 by CPZ. Finally, stable silencing of Egr-1 expression lead to attenuated CPZ-inducible p21(Waf1/Cip1) expression and inhibited G2/M phase cell-cycle arrest. These results demonstrate that a functional link between ERK and JNK MAP kinase pathways and p21(Waf1/Cip1) induction via Egr-1 contributes to CPZ-induced anticancer activity in C6 glioma cells.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-10399797,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-10487524,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-10887152,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-11121417,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-11283270,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-11356306,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-11781575,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-12556466,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-12629205,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-12690110,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-12881433,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-14751836,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-15181148,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-15365258,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-15616591,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-16138117,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-16626293,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-17307334,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-17784215,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-18056463,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-18316600,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-18693247,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-18837915,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-19721135,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-20054233,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-6111102,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-6823028,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-7673138,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-8118801,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-8193547,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-8242751,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-8242752,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-8550239,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-8649519,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-9010223,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-9501095,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20368687-9925742
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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,
http://linkedlifedata.com/resource/pubmed/chemical/Chlorpromazine,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/EGR1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Early Growth Response Protein 1,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1226-3613
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
31
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pubmed:volume |
42
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
395-405
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pubmed:dateRevised |
2010-9-28
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pubmed:meshHeading |
pubmed-meshheading:20368687-Animals,
pubmed-meshheading:20368687-Antineoplastic Agents,
pubmed-meshheading:20368687-Cell Line, Tumor,
pubmed-meshheading:20368687-Cell Proliferation,
pubmed-meshheading:20368687-Chlorpromazine,
pubmed-meshheading:20368687-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:20368687-Early Growth Response Protein 1,
pubmed-meshheading:20368687-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:20368687-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:20368687-Glioma,
pubmed-meshheading:20368687-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:20368687-RNA, Small Interfering,
pubmed-meshheading:20368687-Rats,
pubmed-meshheading:20368687-Transcription, Genetic,
pubmed-meshheading:20368687-Tumor Suppressor Protein p53
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pubmed:year |
2010
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pubmed:articleTitle |
Chlorpromazine activates p21Waf1/Cip1 gene transcription via early growth response-1 (Egr-1) in C6 glioma cells.
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pubmed:affiliation |
Institute of Biomedical Science and Technology, Konkuk University Hospital, Seoul 143-729, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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