Histone deacetylase 1 represses the small GTPase RhoB expression in human nonsmall lung carcinoma cell line.

Abstract

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.

• Authors: Shaowen Wang, Yan Yan-Neale, Denise Fischer, Marija Zeremski, Richard Cai, Jian Zhu, Fred Asselbergs, Garret Hampton, Dalia Cohen
• Journal: Oncogene (Oncogene) Vol. 22 Issue 40 Pg. 6204-13 (Sep 18 2003) ISSN: 0950-9232 [Print] England
• PMID: 13679859 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Bacterial Agents
• CCAAT-Binding Factor
• Enzyme Inhibitors
• Histone Deacetylase Inhibitors
• Peptides
• Repressor Proteins
• trapoxin A
• Monomeric GTP-Binding Proteins
• rhoB GTP-Binding Protein

Topics

• Acetylation (drug effects)
• Anti-Bacterial Agents (pharmacology)
• Base Sequence
• CCAAT-Binding Factor (metabolism)
• Carcinoma, Non-Small-Cell Lung (enzymology, genetics, pathology)
• Cell Line, Transformed
• Enzyme Inhibitors (pharmacology)
• Histone Deacetylase Inhibitors
• Humans
• Lung Neoplasms (enzymology, genetics, pathology)
• Molecular Sequence Data
• Monomeric GTP-Binding Proteins (genetics, metabolism)
• Peptides
• Promoter Regions, Genetic
• Repressor Proteins (antagonists & inhibitors)
• Tumor Cells, Cultured
• Up-Regulation
• rhoB GTP-Binding Protein (genetics, metabolism)