Visit our Expo - Redox and Inflammation signaling 2012

Session XIII : Cell signaling pathways leading to regulated chromatin modifications
Poster XIII, 8
A role for Class I histone deacetylases in proliferation of tumor cells
Silvia Senese 1, Katrin Zaragoza-Dorr 1, Simone Minardi 2, Loris Bernard 2, Giulio F.
Draetta 3, Myriam Alcalay 2, Christian Seiser 4 and Susanna Chiocca 1*
1European Institute of Oncology, Department of Experimental Oncology, 20141 Milan,
Italy,
2 IFOM-IEO Campus, Via Adamello 16, 20139 Milan, Italy, 3 Cancer Research, Merck
Research Laboratories, Basic Research, 33 Avenue Louis Pasteur, Boston, MA 02115,
USA, 4 Department of Medical Biochemistry, Division of Molecular Biology,Medical
University of Vienna, Vienna Biocenter, Dr. Bohr-Gasse 9/2, A-1030 Vienna, Austria
* Corresponding author. Mailing address: European Institute of Oncology, Department
of Experimental Oncology, Via Ripamonti, 435, 20141 Milan, Italy.
Histone deacetylases (HDACs) inhibitors are currently tested in clinical trials as anti-cancer
drugs. Previous studies point towards HDAC1 as one of the possible targets for these tumor
drugs. Therefore, the role of individual Class I HDACs in the regulation of cancer cell
proliferation was investigated using RNAi-mediated protein knockdown. We show here that
ablating HDAC1 and HDAC3 protein expression results in the inhibition of U2OS cell
proliferation and an increase in the percentage of apoptotic cells. On the contrary HDAC2
knockdown shows no effect, unless we concurrently knockdown both HDAC1 and HDAC2.
Moreover, RNAi against HDAC1 alone or in combination with HDAC2 increases the
expression of p21 protein, a cyclin-dependent kinase inhibitor. We also observe that only in
the absence of both HDAC1 and HDAC2 histones H3 and H4 are hyperacetylated. In
addition, HDAC1 knockdown abolishes the ability of cells to reach M phase. Our results
demonstrate that HDAC1 and HDAC3 play a major role in proliferation and survival of tumor
cells and that these HDACs might impair cell cycle progression not only by affecting the
transcription of specific target genes (p21) but also through effects on other important
biological processes.
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