Further tests proved why there was such a small number of receptors. Prof. Krainer: "There can be two reasons for the loss of a receptor molecule like DR4. Firstly, the responsible gene could have been lost or damaged. Secondly, this gene could have been modified in a way which would prevent it from functioning." It was exactly the latter. Prof. Krainer and his team ascertained that in 75% of the specimens which contained only a few DR4 receptors the responsible gene was modified. Some components of this gene were modified by attaching methyl groups. Methylation is indeed a common way in which cells silence genes, but in the affected tumor cells, it obviously happens at the wrong time.
To conclude their research, Prof. Krainer and his colleagues retested their findings: Their results were confirmed by testing 36 different tumor tissues taken directly from patients. In comparison, these cells represent the real causes of disease much better than cell cultures commonly used for experimental research. It was determined that in 20% of the tissues examined the gene responsible for DR4 was methylated to a higher degree and DR4 was missing.
This research supported by funding from the Austrian Science Fund, FWF, paves the way for future therapy through the important discovery that the methylation of the gene for DR4 can contribute to the formation of tumors. These therapies could manipulate the malfunctioning signal transfer system, DR4-TRAIL, to make cancer cells return to the originally programmed cell death.
Image and text will be available online from Wednesday, 15th June 2005, 09.00 a.m. MEZ onwards: http://www.fwf.ac.at/en/press/receptor.html