On thursday february 7th, Sophia Bruggeman will defend her thesis entitled “Polycomb group genes in brain development and cancer: Ink4a/Arf and beyond” in order to receive the degree of doctor (PhD). The ceremony will take place at 14.00 hrs in the Agnietenkapel of the University of Amsterdam. The promoter is Prof. dr. Maarten van Lohuizen.
The thesis describes the research performed to identify the role of two Polycomb group (PcG) genes – Bmi1 and Ring1b – in the development of the central nervous system and brain cancer.
PcG proteins are most well known for their function in patterning of the embryo. They are also powerful repressors of the Ink4a/Arf tumor suppressor locus. This latter characteristic allows them to stimulate cell proliferation. Previously, it has been demonstrated that, if not properly controlled, PcG-mediated Ink4a/Arf repression can contribute to tumor development.
The Ink4a/Arf locus consists of two genes, p16Ink4a and p19Arf. The first part of the thesis deals with the importance of the repression of both two genes by PcG for normal cell proliferation and stem cell maintenance. For this study, a number of different cell types have been used, among which blood and brain cells, and brain tissue. It turned out that p19Arf repression is a prerequisite for all cell proliferation, whereas repression of p16Ink4a is required in a limited number of cases.
The second part of the thesis describes Ink4a/Arf-independent effects of PcG activity, which play a role in the development of glioma, a malignant cancer of the brain. This has been investigated by assaying both glial cells and neural stem cells that are either Ink4a/Arf, or Bmi1 and Ink4a/Arf deficient, for tumor-forming capacity. It is likely that these Ink4a/Arf-independent PcG targets are involved in cellular attachment and differentiation processes.
Altogether, these results highlight that research on PcG proteins should look beyond Ink4a/Arf regulation, as this will increase our understanding of PcG protein activity in development and cancer.