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 Cell Death during Development and Cancer Progression
In the study of programmed cell death, or apoptosis, Michael Hengartner's lab has made significant progress in identifying the genes involved and their roles. Working with postdoctoral researcher Mona Spector, Michael has continued to gain new information about this process by studying the tiny worm Caenorhabditis elegans, an ideal model organism for genetics research. Previously, three genes were known to be essential for properly controlled programmed cell death to take place in C. elegans, and two of these genes were known to have counterparts, or homologs, in mammals. Michael and others had shown that CED-3 and CED-4 work in concert to kill unneeded cells, a necessary process cells during normal development, and that CED-9 suppresses this action. If the worm carries a mutation in either CED-3 or CED-4, then this necessary mechanism to rid the body of unwanted cells never takes place, resulting in excess cells in the adult worm. In contrast, if there is a mutation in CED-9, programmed cell death is not controlled and cells die at an abnormally high rate.
Recently, Michael and Mona identified a previously unknown physical interaction between the suppressor of cell death, CED-9, and the activator of cell death, CED-4. They discovered that if the interaction between the two proteins is disrupted, there is a failure to control apoptosis. These and other results suggest that CED-9 works by binding to CED-4 and regulating its activity. The new information begins to suggest how CED-3, 4, and 9 interact to control the process of programmed cell death.
Many drugs for treating cancer kill tumor cells by inducing apoptosis, or programmed cell death, but many tumor cells have mutations that produce resistance to chemotherapy. Yuri Lazebnik and Scott Lowe have been studying the process of cell death in normal and tumor cells and they reported this year that unexpectedly, extracts from drug-resistant tumor cells contain the cell death machinery and the ability to trigger this process. Interestingly, the tumor cells contain an activity that can induce programmed cell death in normal cells, a factor that Yuri and Scott call oncogene-generated activity (OGA). They are pursuing the nature of OGA with the hope that they might be able to stimulate its function in tumor cells that have become resistant to chemotherapy.
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