Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
40
pubmed:dateCreated
2003-9-18
pubmed:abstractText
The dynamic balance between histone acetylation and deacetylation plays a significant role in the regulation of gene transcription. Much of our current understanding of this transcriptional control comes from the use of HDAC inhibitors such as trapoxin A (TPX), which leads to hyperacetylated histone, alters local chromatin architecture and transcription and results in tumor cell death. In this study, we treated tumor cells with TPX and HDAC1 antisense oligonucleotides, and analysed the transcriptional consequences of HDAC inhibition. Among other genes, the small GTPase RhoB was found to be significantly upregulated by TPX and repressed by HDAC1. The induction of RhoB by HDAC inhibition was mediated by an inverted CCAAT box in the RhoB promoter. Interestingly, measurement of RhoB transcription in approximately 130 tumor-derived cell lines revealed low expression in almost all of these samples, in contrast to RhoA and RhoC. Accumulating evidence indicates that the small GTPase Rho proteins are involved in a variety of important processes in cancer, including cell transformation, survival, invasion, metastasis and angiogenesis. This study for the first time demonstrates a link between HDAC inhibition and RhoB expression and provides an important insight into the mechanisms of HDAC-mediated transcriptional control and the potential therapeutic benefit of HDAC inhibition.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6204-13
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:13679859-Acetylation, pubmed-meshheading:13679859-Anti-Bacterial Agents, pubmed-meshheading:13679859-Base Sequence, pubmed-meshheading:13679859-CCAAT-Binding Factor, pubmed-meshheading:13679859-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:13679859-Cell Line, Transformed, pubmed-meshheading:13679859-Enzyme Inhibitors, pubmed-meshheading:13679859-Histone Deacetylase Inhibitors, pubmed-meshheading:13679859-Humans, pubmed-meshheading:13679859-Lung Neoplasms, pubmed-meshheading:13679859-Molecular Sequence Data, pubmed-meshheading:13679859-Monomeric GTP-Binding Proteins, pubmed-meshheading:13679859-Peptides, pubmed-meshheading:13679859-Promoter Regions, Genetic, pubmed-meshheading:13679859-Repressor Proteins, pubmed-meshheading:13679859-Tumor Cells, Cultured, pubmed-meshheading:13679859-Up-Regulation, pubmed-meshheading:13679859-rhoB GTP-Binding Protein
pubmed:year
2003
pubmed:articleTitle
Histone deacetylase 1 represses the small GTPase RhoB expression in human nonsmall lung carcinoma cell line.
pubmed:affiliation
Department of Functional Genomics, Novartis Pharmaceutical Corporation, East Hanover, Summit, NJ 07901, USA.
pubmed:publicationType
Journal Article, Comparative Study