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

Oncogene volume 22, pages 6204–6213 (2003)Cite this article

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 ∼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.

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Acknowledgements

We thank R Kramer for reviewing the manuscript, and E Verdin for providing HDAC6 expression vector (Chen et al., 2001b).

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Authors and Affiliations

  1. Department of Functional Genomics, Novartis Pharmaceutical Corporation, East Hanover, Summit, 07901, NJ, USA

    Shaowen Wang, Yan Yan-Neale, Denise Fischer, Marija Zeremski, Richard Cai, Jian Zhu, Fred Asselbergs & Dalia Cohen

  2. Genomics Institute of the Novartis Research Foundation, San Diego, 92121, CA, USA

    Garret Hampton

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  1. Shaowen Wang
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Correspondence to Dalia Cohen.

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Wang, S., Yan-Neale, Y., Fischer, D. et al. Histone deacetylase 1 represses the small GTPase RhoB expression in human nonsmall lung carcinoma cell line. Oncogene 22, 6204–6213 (2003). https://doi.org/10.1038/sj.onc.1206653

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