Many genes involved in the control of G1-to-S phase transition as well as in the metabolism of DNA synthesis are under transcriptional regulation by the E2F family of transcription factors, particularly, by E2F1. On the other hand, E2F1 also plays a role as a tumor suppressor in certain tissues (Field, Cell 1996, 85:549-61; Yamasaki et al., Cell 1996, 85:537-48) owing to its ability to induce apoptosis in some cell types (Bell & Ryan, Cell Death Differ 2004, 11:137-42). Our goal with this project is to understand the regulatory mechanisms that discriminate E2F1 as a cell cycle gene or as a pro-apoptotic/tumor suppressor gene in cancer cells, so that we are seeking to identify the mechanisms that activate E2F1 function in cancer models of cell apoptosis. Our hypothesis is that induction of pro-apoptotic E2F1 might be impaired during tumor progression of some cancer cells, which would then acquire survival advantage in response to apoptotic stimuli. Identifying molecular alterations in E2F1-mediated apoptosis may help to predict the behavior of tumors in response to treatments, as well as provide novel putative targets for therapy.
Schematic representation of our working hypothesis on the dual role of E2F1 in the control of cancer cell cycle and apoptosis.
Contact: Xavier Mayol, xmayol@imim.es, tel 93.316.04.24, fax 93.316.04.10.
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