Role for histone deacetylase 1 in human tumor cell proliferation

Silvia Senese, Katrin Zaragoza, Simone Minardi, Ivan Muradore, Simona Ronzoni, Alfonso Passafaro, Loris Bernard, Giulio F. Draetta, Myriam Alcalay, Christian Seiser, Susanna Chiocca

Research output: Contribution to journalArticle

176 Citations (Scopus)

Abstract

Posttranslational modifications of core histones are central to the regulation of gene expression. Histone deacetylases (HDACs) repress transcription by deacetylating histones, and class I HDACs have a crucial role in mouse, Xenopus laevis, zebra fish, and Caenorhabditis elegans development. The role of individual class I HDACs in tumor cell proliferation was investigated using RNA interference-mediated protein knockdown. We show here that in the absence of HDAC1 cells can arrest either at the G1 phase of the cell cycle or at the G2/M transition, resulting in the loss of mitotic cells, cell growth inhibition, and an increase in the percentage of apoptotic cells. On the contrary, HDAC2 knockdown showed no effect on cell proliferation unless we concurrently knocked down HDAC1. Using gene expression profiling analysis, we found that inactivation of HDAC1 affected the transcription of specific target genes involved in proliferation and apoptosis. Furthermore, HDAC2 downregulation did not cause significant changes compared to control cells, while inactivation of HDAC1, HDAC1 plus HDAC2, or HDAC3 resulted in more distinct clusters. Loss of these HDACs might impair cell cycle progression by affecting not only the transcription of specific target genes but also other biological processes. Our data support the idea that a drug targeting specific HDACs could be highly beneficial in the treatment of cancer.

Original languageEnglish
Pages (from-to)4784-4795
Number of pages12
JournalMolecular and Cellular Biology
Volume27
Issue number13
DOIs
Publication statusPublished - Jul 2007

Fingerprint

Histone Deacetylases
Cell Proliferation
Neoplasms
Histones
Cell Cycle
Biological Phenomena
Caenorhabditis elegans
Xenopus laevis
G1 Phase
Gene Expression Regulation
Gene Expression Profiling
Zebrafish
Drug Delivery Systems
Post Translational Protein Processing
RNA Interference
Genes
Down-Regulation
human HDAC1 protein
Apoptosis
Growth

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Senese, S., Zaragoza, K., Minardi, S., Muradore, I., Ronzoni, S., Passafaro, A., ... Chiocca, S. (2007). Role for histone deacetylase 1 in human tumor cell proliferation. Molecular and Cellular Biology, 27(13), 4784-4795. https://doi.org/10.1128/MCB.00494-07

Role for histone deacetylase 1 in human tumor cell proliferation. / Senese, Silvia; Zaragoza, Katrin; Minardi, Simone; Muradore, Ivan; Ronzoni, Simona; Passafaro, Alfonso; Bernard, Loris; Draetta, Giulio F.; Alcalay, Myriam; Seiser, Christian; Chiocca, Susanna.

In: Molecular and Cellular Biology, Vol. 27, No. 13, 07.2007, p. 4784-4795.

Research output: Contribution to journalArticle

Senese, S, Zaragoza, K, Minardi, S, Muradore, I, Ronzoni, S, Passafaro, A, Bernard, L, Draetta, GF, Alcalay, M, Seiser, C & Chiocca, S 2007, 'Role for histone deacetylase 1 in human tumor cell proliferation', Molecular and Cellular Biology, vol. 27, no. 13, pp. 4784-4795. https://doi.org/10.1128/MCB.00494-07
Senese S, Zaragoza K, Minardi S, Muradore I, Ronzoni S, Passafaro A et al. Role for histone deacetylase 1 in human tumor cell proliferation. Molecular and Cellular Biology. 2007 Jul;27(13):4784-4795. https://doi.org/10.1128/MCB.00494-07
Senese, Silvia ; Zaragoza, Katrin ; Minardi, Simone ; Muradore, Ivan ; Ronzoni, Simona ; Passafaro, Alfonso ; Bernard, Loris ; Draetta, Giulio F. ; Alcalay, Myriam ; Seiser, Christian ; Chiocca, Susanna. / Role for histone deacetylase 1 in human tumor cell proliferation. In: Molecular and Cellular Biology. 2007 ; Vol. 27, No. 13. pp. 4784-4795.
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