gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

A role for E2F3 in cellular migration and onset of metastasis

Meeting Abstract

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  • corresponding author presenting/speaker Caroline Boden - Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch, Deutschland
  • Ulrike Ziebold - Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO410

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Veröffentlicht: 20. März 2006

© 2006 Boden et al.
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The E2F-family of transcription factors are key downstream targets of the retinoblastoma tumorsuppressor, pRB. E2F3, one member of the E2F-family plays a critical role in mitogen-induced cell cycle re-entry and activation of E2F target genes. In a previous study, we have shown that loss of E2F3 dramatically increases both the tumor onset as well as the incidence of metastases in Rb+/- mice. Since altered adhesive and invasive properties are believed to be a pre-requisite for metastasis, we questioned if E2F3 participates in these processes. Therefore, we have used our mouse model to establish embryonic fibroblasts (MEFs) devoid of pRb and E2F3 function. Using these MEFs we have performed adhesion, wound-healing, Boyden chamber assays and gene expression profiling. In addition, we used our Rb+/-;E2f3-/- mutant mice and collected medullary thyroid carcinomas (MTCs) to separate metastatic and non-metastatic MTCs in a microarray analysis. Comparing the results of both MEF and MTC microarrays enabled us to identify new target genes of the pRB-E2F pathway. The increased incidence of metastasis found in Rb+/-;E2f3-/- mutant mice, ultimately suggest to us that E2F3 is important for cellular adhesion, migration and invasion. Using this approach we have identified direct E2F-target genes with a potential role in tumor progression and metastasis.