Gene plays major role in formation of stem cells and cancer

Researchers from the Netherlands Cancer Institute in Amsterdam have discovered a common link between cancer cells and stem cells. Together with colleagues from the University of Zurich, Merel Lingbeek and NWO pioneer Prof. Maarten van Lohuizen published their findings on 18 March 2004 in Nature.

Because cancer cells and stem cells can both reproduce themselves in unlimited numbers, it was suspected that they have something in common. That suspicion proved to be correct. Together with their Swiss colleagues, researchers from the Netherlands Cancer Institute discovered an important common link: the BMI1 gene.

Stem cells, the ’original cells’, develop into specialised body cells by first of all making many copies of themselves. Once this copying process has been completed, they stop dividing and start differentiating into specialised cells, for example, a brain cell. But sometimes this process goes wrong. Instead of differentiating, the stem cells retain the expression pattern of a stem cell and keep on copying themselves. This is how medulloblastomas, the most frequently occurring form of brain cancer in children, can develop.

Determining stem cell identity

The publication in Nature reveals that the BMI gene plays a crucial role in this switching process. Together with Swiss colleagues Carly Leung and Silvia Marino, Merel Lingbeek and Prof. Maarten van Lohuizen investigated the formation of brain cells from stem cells in the cerebellum.

The research revealed that the BMI1 gene is essential for the multiplication of the stem cells in the cerebellum. Further it was found that overexpression of the BMI1 gene can result in an enormous growth of these stem cells. For example, overexpression of the BMI1 gene was found in 8 of the 12 medulloblastomas investigated. The BMI1 gene was found to determine the identity of the stem cell: the gene ensures that a stem cell remains a stem cell and does not differentiate. The researchers therefore suspect that an overexpression of the BMI1 gene contributes to the development of these brain tumours.

Subsequent research

The researchers expect that the BMI1 gene plays a role in other types of cancer with stem-cell-like characteristics, including breast tumours and leukaemia. These assumptions will be investigated in subsequent research, which will also examine whether key regulators such as the BMI1 gene can be influenced by drugs.

The research was funded by the Netherlands Organisation for Scientific Research.