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MedUni Vienna researchers discover “bodyguard” for cancer cells

(Vienna, 31 March 2011) A team of researchers at MedUni Vienna has managed to decipher a mechanism which solely protects cancer cells and helps them grow. This means a therapeutic approach is possible which specifically attacks tumour cells without damaging healthy cells.

Tumour cells use many different methods to prevent their own cell death and to grow quickly. Special proteins, so-called transcription factors, play a decisive role here. There are many of these in most tumours and they contribute to the degeneration of cells.

One such transcription factor is c-Jun. In their study Veronika Sexl and her team have deciphered a new mechanism for how c-Jun accelerates tumour growth. C-Jun is not only able to activate genes, by “docking” to the DNA it also prevents epigenetic changes to a tumour cell and therefore also the deactivation of genes which regulate growth. C-Jun therefore acts as a kind of bodyguard for “growth genes” and enables cells to quickly proliferate.

One gene which is particularly protected by c-Jun is the cell cycle kinase Cdk6. This is very often found in tumours of the blood-forming system in particular. In a mouse model the researchers have now proved that Cdk6 is crucial for the growth of degenerated cells but hardly influences healthy blood cells. This connection was also discovered for the first time.

Corresponding medicines which inhibit the activity of Cdk6 are currently being developed and are also already being tested in clinical trials. They would make it possible to specifically target this gene in the treatment and therefore prevent tumour growth without damaging healthy cell tissue.

This study headed by Univ. Prof. Dr. Veronika Sexl from the Centre for Physiology and Pharmacology at MedUni Vienna has been conducted in cooperation with Ao. Univ. Prof. Dr. Sabine Zöchbauer-Müller from Department of Medicine I and Mag. Priv. Doz. Dr. Martin Bilban from the Division of Medical and Chemical Laboratory Diagnostics of MedUni Vienna’s Comprehensive Cancer Centre with support from the Cell Division and Cancer Group, Molecular Oncology Programme, Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid, Spain.The study director Veronika Sexl has headed the Institute of Pharmacology and Toxicology at the Vienna University of Veterinary Medicine (Vetmeduni Vienna) since 1 December 2010. Lead author Karoline Kollmann and co-author Christine Schneckenleithner have also been at Vetmeduni Vienna since 1 January 2011.

The study will appear in the upcoming edition of the international specialist journal “Blood”:
» C-JUN promotes BCR-ABL induced lymphoid leukemia by inhibiting methylation of the 5' region of Cdk6
Karoline Kollmann, Gerwin Heller, Rene Georg Ott, Ruth Scheicher, Eva Zebedin-Brandl, Christine Schneckenleithner, Olivia Simma, Wolfgang Warsch, Eva Eckelhart, Andrea Hoelbl, Martin Bilban, Sabine Zöchbauer-Müller, Marcos Malumbres and Veronika Sexl
DOI 10.1182/blood-2010-07-299644.