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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-10-11
pubmed:abstractText
Histone deacetylase (HDAC) inhibitors have shown promise in clinical cancer therapy and to consistently induce p21WAF1/CIP1 expression in a p53-independent manner and via increased acetylation of the chromatin at the Sp1 sites in the p21WAF1/CIP1 promoter region. However, the exact mechanism by which HDAC inhibitors induce p21WAF1/CIP1 remains unclear. In this study, we observed that Trichostatin A (TSA), a HDAC inhibitor, induced strikingly p21WAF1/CIP1 expression in human cervical cancer (HeLa) cells, and this induction correlated with downregulation of c-myc expression. Coincident with this observation, knock down of c-myc with a c-myc specific small interfering RNA dramatically induced expression of p21WAF1/CIP1 in these cancer cells. These data suggest that c-myc may play a critical role in repression of p21WAF1/CIP1 expression in HeLa cells. More importantly, using chromatin immunoprecipitation assay, we observed for the first time that c-myc bound to the endogenous p21WAF1/CIP1 promoter in untreated HeLa cells, but not in TSA-treated cells. Taken together, TSA induced c-myc downregulation and release from the endogenous p21WAF1/CIP1 promoter contributes, at least partially, to transcriptional activation of the p21WAF1/CIP1 in HeLa cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor..., http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering, http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53, http://linkedlifedata.com/resource/pubmed/chemical/trichostatin A
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
324
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
860-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15474507-Blotting, Western, pubmed-meshheading:15474507-Cell Cycle Proteins, pubmed-meshheading:15474507-Cell Line, Tumor, pubmed-meshheading:15474507-Chromatin Immunoprecipitation, pubmed-meshheading:15474507-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:15474507-Down-Regulation, pubmed-meshheading:15474507-Enzyme Activation, pubmed-meshheading:15474507-Enzyme Inhibitors, pubmed-meshheading:15474507-Female, pubmed-meshheading:15474507-HeLa Cells, pubmed-meshheading:15474507-Histone Deacetylase Inhibitors, pubmed-meshheading:15474507-Humans, pubmed-meshheading:15474507-Hydroxamic Acids, pubmed-meshheading:15474507-Promoter Regions, Genetic, pubmed-meshheading:15474507-Protein Synthesis Inhibitors, pubmed-meshheading:15474507-Proto-Oncogene Proteins c-myc, pubmed-meshheading:15474507-RNA, Small Interfering, pubmed-meshheading:15474507-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15474507-Sp1 Transcription Factor, pubmed-meshheading:15474507-Transcription, Genetic, pubmed-meshheading:15474507-Transcriptional Activation, pubmed-meshheading:15474507-Transfection, pubmed-meshheading:15474507-Tumor Suppressor Protein p53, pubmed-meshheading:15474507-Uterine Cervical Neoplasms
pubmed:year
2004
pubmed:articleTitle
Histone deacetylase inhibitor, Trichostatin A, activates p21WAF1/CIP1 expression through downregulation of c-myc and release of the repression of c-myc from the promoter in human cervical cancer cells.
pubmed:affiliation
Institute of Medical Virology, Wuhan University School of Medicine, Wuhan, Hubei 430071, PR China. huilee6@yahoo.com
pubmed:publicationType
Journal Article