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Brain tumors: Tissue stem cell turning into tumor stem cell
Date:4/1/2010

The "cradle" of new neurons in the adult brain is well known. It is what is called the subventricular zone, a tissue structure lining the lateral ventricles. This is where neural or brain stem cells reside, which are responsible for generating new neurons if needed. For many years now, the subventricular zone has been suspected to be the origin of specific malignant brain tumors called gliomas, the most deadly type of which is glioblastoma.

Scientists from the divisions of Professor Dr. Gnther Schtz and Professor Dr. Peter Lichter at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have recently shown in mouse brains that brain stem cells in the subventricular zone are characterized by a specific molecule: Protein Tlx, a transcription factor, which stimulates the activity of various genes. In the adult animal, Tlx is expressed exclusively in brain stem cells. When the scientists switched off Tlx, there were no more detectable stem cells in the brain and the formation of new neurons ceased. Functioning of the stem cells thus appears to depend on the presence of this protein.

In their recent study, the teams headed by Gnther Schtz and Peter Lichter, jointly with Professor Dr. Guido Reifenberger of Dsseldorf University, have now tested the opposite case: What happens if the production of Tlx is increased? Using a molecular-biological trick, the investigators induced an overproduction of Tlx by the brain stem cells of mice. As a result, cell division activity in the subventricular zone increased, the cells left their habitual environment called stem cell niche, and started forming glioblastoma-like tissue lesions. In another experiment in which the researchers additionally switched off the p53 protein as an important cancer brake, invasively growing glioblastomas arose from the cancer precursors.

Moreover, the scientists discovered that stem cells with increased Tlx production stimulate the formation of new vess
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Contact: Dr. Sibylle Kohlstdt
s.kohlstaedt@dkfz.de
Helmholtz Association of German Research Centres
Source:Eurekalert

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