The role of the forkhead transcription factor FOXP1 in cancer.

Cancer development is directly related to genetic defects such as chromosomal instability and mutations in the baseline genome. As a consequence of these genetic aberrations, transcriptional and translational processes are disturbed and result in dysregulated expression of a number of survival- and proliferation-related proteins, whichs constitutive activation may result in uncontrolled cell proliferation and thus cancer development. One of these cancer-related translocations, t(3;14)(p13;q32), was identified in a particular subset of Bcell lymphomas and results in rearrangement of the forkhead box protein P1 gene (FOXP1). Although FOXP1 expression has a drastic impact on clinical outcome in lymphomas, little is known about how FOXP1 determines and influences cancer biology. To clarify this issue, we plan (1) to quantify FOXP1 expression in human cancer tissue and assess molecular mechanisms underlying altered FOXP1 expression, (2) to analyze in vitro the mechanism of action of FOXP1 in tumor derived cell lines and their non-neoplastic counterpart ; (3) to develop a transgenic FOXP1 mice model to investigate in vivo the role of FOXP1 in lymphoma pathogenesis. The outcome of this research project may significantly add to what is currently known in the field, and test the viability of FOXP1 as a therapeutic target.

Keywords:Cellines, Transgene mice model, Cancer, FOXP1, FISH, RT-PCR, Mutation-analysis

Disciplines:Morphological sciences, Oncology, Systems biology, Hematology, Laboratory medicine