BBB seminar: Varda Rotter
Identification and characterization of p53-associated “gene signatures” involved in cellular transformation
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
As it is well accepted that malignant transformation is a stepwise process, it is challenging to discover which of these steps involve the p53 tumor suppressor protein. To that end we have established several in-vitro transformation models in which normal cells were transformed into cancer cells by well-controlled genetic alterations. In our experiments, we have immortalized various human primary cells of lung and prostate origin and engineered into them several defined cancer-associated genetic alterations. These included inactivation of p53 by several methods, over-expression of mutant p53, over-expression of the Ras oncogene and various combinations of these modifications. As a result we have obtained transformed cells that are capable of developing into tumors in mice, suggesting that the in-vitro developed system represents an authentic model of cancer development. To characterize the gene networks that are associated with the defined malignant steps, we have used a genome-wide approach, which permits the identification of gene signatures that are associated with the individual steps of malignant transformation.
In general it seems that the clusters that we have identified and analyzed using this in-vitro model agree with specific steps of transformation and thus may serve as specific hallmark signature s of tumorigenesis.
Chair : Karl-Henning Kalland <Kalland@gades.uib.no>, The Gade Institute