Moleculaire mechanismen van tumor suppressie door de atonal transcriptie factor.

In this proposal we plan to identify novel regulators of carcinogenesis from a among a subset of approximately 40 genes that we have identified as transcriptional targets or genetic interactors of the Atonal tumor suppressor gene. We will begin by screening all these genes in a powerful Drosophila of tumor formation, progression and metastasis. Genes that score positive for one or more aspects of tumor growth in this screen will be tested for expression, gain of function and loss of function in human cancer cell lines. Finally, a select group of genes positive in this second set of assays will be tested for expression levels and mutations in human cancer patients. These studies will lead to three important findings. First, they will unravel the detailed molecular mechanisms of the Atonal tumor suppressor pathway. Second, they will identify novel putative oncogenes and or tumor suppressor genes for further validation in in vivo mammalian cancer models.

Trefwoorden:Molecular biology, Oncology, Molecular mechanism of tumor