Janus faces of ras: anti or pro-apoptotic?
Cell population homeostasis is a balance between cell proliferation on one hand and the rate of cell loss on the other hand. Normal tissue homeostasis requires the physiological deletion of cells by activation of apoptosis, a genetically determined program of autonomous cell death. ras is most probably the most important oncogene in human cancer. It is mutated in 30% of all tumors especially those of the gastrointestinal tract. In regulating apoptosis ras has many faces. it has both negative and positive effects depending on the stimulation and cell type. The responses of cells to ras signaling depends on the level of Ras expression, the activity of various pathways, and which of the cell cycle check points are functioning. New farnesyl transferase inhibitors and non-steroidal anti-inflammatory compounds may provide a new strategy for novel therapeutic modalities in the treatment of human cancer. The first clinical trials have been initiated, preliminary results are promising, although no firm results are yet available.
Arber
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Department of Gastroenterology, GI Oncology Unit, Tel Aviv Sourasky Medical Center and Tel Aviv University, 64239 Tel Aviv, Israel. narber@post.tau.ac.il