16 December 2014

Danish researchers find new anti-cancer gene

Cancer research

To avoid cancer it is crucial that division of our cells is closely controlled. Researchers from BRIC, University of Copenhagen, and the Department of Haematology at Rigshospitalet show that a previously undescribed gene, PRDM11, inhibits the growth of blood cancer cells. The results are published in the international journal Blood.

In order to maintain the body functions and prevent disease, it is crucial that the activity of our genes is closely regulated. This regulation is carried out by so-called transcription factors that either inhibit or stimulate the activity of our genes. A group of these inhibitors are known as tumor suppressors, as one of their tasks is to inhibit the activity of specific genes that causes uncontrolled growth of cancer cells.

- Our new results identify PRDM11 as an important new tumor suppressor in a specific type of lymphatic cancer. This knowledge is important in order to understand how cancer occurs and develops and may also be used to predict the course of disease, says professor Anders H. Lund, BRIC, who headed the research.

PRDM11 suppresses the activity of cancer genes

cancer cell colonies (purple spots when cultured cells lack PRDM11).

Cells lacking PRDM11 easier develops into cancer cells because cancer genes such as MYC are given a clear field. This is evident from the experiments demonstrating an increase in more cancer cell colonies (purple spots when cultured cells lack PRDM11. Photo: Cathrine Fog-Tonnesen

In a large screening test PRDM11 turned up as a possible new tumor suppressor. In order to test this hypothesis, the researchers developed a mouse model where the PRDM11 gene was removed.

- By removing the PRDM11 gene in a mouse model for lymphatic cancer we were able to see that the development of cancer was accelerated. This shows that PRDM11 usually protects against cancer development and therefor can be categorized as a tumor suppressor. We also found that PRDM11 works by inhibiting the activity of selected genes, including several known cancer stimulating genes which PRDM11 usually suppresses, explains postdoc and senior researcher Cathrine Fog-Tonnesen, who was the driving force behind the experimental investigations. 

Blood cancer patients without PRDM11 lives shorter lives

The basic research discovery made by the researchers is consistent with their studies of patients with the type of lymphatic cancer called diffuse large B-cell lymphoma which approximately 400 Danes are diagnosed with each year. These cancer patients turned out to have a shorter survival if they lacked PRDM11. Probably because PRDM11 is not able to inhibit cancer genes, which makes the growth of cancer cells more aggressive. 

Staining of PRDM11 (brown color) in tumors from patients with diffuse large B-lymphoma.

Staining of PRDM11 (brown color) in tumors from patients with diffuse large B-lymphoma. Some patients lack PRDM11 in cancer cells (left) and have shorter survival expectancy, probably because the lack of PRDM11 makes their form of cancer more aggressive. Photo: Elisabeth Ralfkiær.

- Our results suggest that PRDM11 can be used to predict the level of aggressiveness of a patient’s lymphatic cancer. This knowledge may be important for future planning of effective individual treatments, says professor and chief physician Kirsten Grønbæk, who is responsible for the clinical studies.

The researchers from BRIC and the Department of Haematology at Rigshospitalet collaborate closely, which enables basic research results to be tested for clinical relevance and for clinical problems to be investigated at a mechanistic level in the laboratories. 

- Such an interdisciplinary collaboration is crucial in order to successfully pursue cancer research and for the development of new targeted treatments and is a priority for both our departments, says Anders H. Lund and Kirsten Grønbæk. 

The research is supported by the Danish Council for Independent Research, the Danish Cancer Society, Association for International Cancer Research and the Novo Nordisk Foundation.