Leuven geneticists discover switch to turn cancer on and off
Perspectives for new treatment
Luc West
In collaboration with American colleagues, Wouter Bossuyt from the VIB Laboratory for Neurogenetics headed by Bassem Hassan, has discovered how a particular gene causes cancer of the large intestine, or colon.
The cancer develops when the gene is switched off. If the gene is switched back on again, the cancer stops growing and the malignant cells disappear. The experiment was successful in ‘in vitro’ human cancer cells in cell cultures in the laboratory. The next step is to investigate whether the gene can be switched on again ‘in vivo’, in intestinal cancer patients themselves.
Each gene carries information about a specific hereditary characteristic. In effect, genes are switches, they can either be ‘on’ or ‘off’ and this determines the course of processes in the cells. The so-called ‘atonal’ genes guide the process of cell differentiation. In a manner of speaking, these are the main switches: if they are ‘on’, they ensure that cells develop into specific types of cells, such as skin cells, nerve cells, bone cells, liver cells, brain cells, etc. and that their separation is controlled. Cancer cells are cells that are less differentiated. They have no specific function and their separation is uncontrolled: thus, they proliferate rampantly. That is how tumours come into existence. Until now, however, it has been unclear whether the loss of differentiation was a cause or a consequence of tumours.
Wouter Bossuyt and Bassem Hassan have demonstrated that a tumour can indeed be one of the consequences of a lack of differentiation. They have succeeded in doing this in the cells of fruit flies, mice and even humans. In the fruit fly, they demonstrated that switching the ‘atonal’ gene of the eye off, causes cancer of the eye. When they switched the ‘atonal’ gene on again, the uncontrolled cell separation stopped and the undifferentiated cells died. Not only did the tumour stop growing, it simply disappeared.
In the cells of mice and humans they concentrated on the human variant of the ‘atonal’ gene, ATOH1. This gene is involved in the development of two types of cancer: Merkel cell carcinoma, an aggressive skin cancer which is rare and cancer of the large intestine, which is much more common. In the large intestine, ATOH1 causes cells to specialise into slime cells in the intestinal wall.
What did they discover? When ATOH1 is switched off in the large intestine of mice, the cells form polyps and the mice develop cancer of the large intestine. The researchers also discovered that frequently, ATOH1 does not work in humans who suffer from cancer of the large intestine. Thus, Bossuyt and Hassan are the first to prove that there is a connection between the functioning of ‘atonal’ genes and the development of tumours.
Furthermore, for clinical applications, it is of equal importance that they have succeeded in reactivating an ATOH1 gene that was switched off and that they did so using a fairly simple chemical substance. Now that they have achieved this in human cell cultures in a laboratory, it is very possible that they have paved the way to a cure for intestinal cancer.
Online: http://med.kuleuven.be/cme-mg/
