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Content archived on 2024-05-29

A systematic approach to find new cancer molecules: an enhancer trap screen to identify


The main objective of this proposal is to find new molecules and define mechanisms involved in human tumourigenesis. Developing new ways to combat cancer is a major task for researchers giving hope to the community as a whole. Therefore, we will embark on aiding the detection of tumours by searching for novel marker genes and discovering new mechanisms.

To do this, we will use a gene-trap screen in murine embryonic stem cells (mES). Then, we will molecularly dissect the phenotypic changes from undifferentiated to differentiated mES-cells and analyse in detail all transcriptional changes that happen in this transition phase using DNA-chip micro-array screen. Results of both screens will be used to test potential candidates in vivo.

Using a genetically defined mouse model that develops aggressive tumours that metastasize to numerous organs, we are able to pre-screen candidates. Mutant mES-lines of our gene-trap screen enable us to directly assess in vivo function of promising candidates in the mouse (chimaera and germline-mutants).

Hereafter of all promising candidates the relative expression and activity will be tested in human normal cells and human biopsies. Screen a human tumour bank will allow us to make a definite statement if these genes influence primary to secondary tumour progression.

Ultimately, we wish to test the hypothesis if there are molecules and mechanisms that innately connect the control of stem cell proliferation and differentiation with the initiation and progression of tumours.

Thus, our project w ill also provide progress to the field of stem-cell biology. A better knowledge of these mechanisms and the possibility to find novel molecules might transform our view of tumourigenesis and embryonic stem cells.

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