‘Overactive protein can lead to tumour formation’
Kristiaan Lenos has investigated the working of the Hdmx protein, which is indirectly involved in the development of cancer. 'Thanks to this research, patients can receive a more specific treatment and a more reliable prognosis regarding their survival chances,’ says the young researcher.
Survival chances
A tumour which developed as a result of an ‘overactivation’ of the Hdmx protein in human cells
According the Lenos, the research has furthered our knowledge of the processes which influence the growth of tumours. Lenos’ conclusion: ´The excessive presence of Hdmx can lead to the formation of tumours and a worse response to chemotherapy treatment. In addition, the increased presence of certain forms of Hdmx is a good indicator for a prognosis of the survival chances of a patient. The result is that a patient can receive a more specific treatment and a more reliable prognosis regarding his or her survival chances.'
DNA damage
Our bodies are the theatre of an almost constant process of cell division. With each cell division, DNA is doubled and divided over the daughter cells. In the course of this process, known as replication, the DNA is checked for errors and possible damage, because changes in the DNA can be harmful for the cell and for the organism as a whole. If an error is discovered, the entire DNA doubling process is interrupted, and will only resume once the damage has been repaired.
Directing
An important pivot in this control system is the protein p53. In normal, healthy, growing cells, this protein does not do much. But once damage to the DNA has been established, p53 wakes up. Depending on the degree of damage, p53 directs further processes, varying from interrupting cell division to instigating the death of the cell. And this is a very important function, because in this way, the growth of tumours can be stopped.
Guarding
However, the interruption of cell division, or the instigation of the death of the cell, may only take place in emergency cases. Which is why the controller p53 has in turn two safeguards, the proteins Hdm2 and Hdmx. These two proteins ensure that the amount of active p53 remains low under normal circumstances.
Impeding
In earlier research into different types of tumour, something suspicious kept coming to light: a high level of activity of Hdmx. The suspicion was that in these cases, the protein impeded the functioning of p53, which was supposed to prevent the increase in tumour cells.
Inactivation
Kristiaan Lenos
This was the reason for researcher Kristiaan Lenos to investigate the function and regulation of Hdmx. Using molecular biological techniques, he ´inactivated´ various forms of the Hdmx protein in the tumour samples of patients. He then observed the reaction of the tumour cells, in combination with various drugs. He also discovered that healthy cells can change into tumour cells if the quantity of active Hdmx protein increased.
After his defence, Lenos will continue to work as researcher in the field of tumour biology, as a postdoc at the VUmc in Amsterdam.
Defence
Wednesday 21 December 2011, 13:45
Kristiaan Lenos
title: Functions and Regulation of Hdmx and Post-Translational Modifications in Drug Sensitivity and Cancer
Medicine
Thesis supervisor: Prof. P. ten Dijke
(22 December 2011/ Jan Joost Aten)