Professor Dr. Christian Seiser from the Division of Molecular Genetics at MedUni Vienna has discovered that epigenetic changes such as the loosening or condensation of the package of specific genes play a major role in the development of cancer diseases. The findings were published in the latest issue of "Molecular and Cellular Biology".
Jointly with his group from Max F. Perutz Laboratories he studied the histone deacetylases required for this purpose that compress chromatin locally by deacetylation.
It became apparent that histone deacetylase HDAC1 is of major importance for the maintenance of cell growth. "In a mouse model system, the loss of HDAC1 leads to a proliferation defect of embryonal stem cells and fibroblasts," explains Seiser. In addition, the tumour suppressor p21 is more strongly expressed. If it is switched off, this cancels out the growth effect.
The group was able to show in cooperation with the team around Patrick Matthias from the Friedrich Miescher Institute in Basel that "the joint loss of HDAC1 and the homologous enzyme HDAC2 completely inhibits cell growth". The outcome of this cooperation has just been published in the top journal "Genes & Development". Histone deacetylase inhibitors such as vorinostat inhibit the proliferation of tumour cells and are already being tested in clinical trials as cancer medication. "However at the moment it is not yet clear which of the 18 deacetylases present in human cells are of relevance for the therapeutic effect," says Seiser. The new results identify HDAC1 and HDAC2 as potentially important targets for cancer therapy.
