Complementation Screening in Mammalian Cells: Application to Cell Immortalization.
Annual rept. 1 Sep 97-31 Aug 98,
COLD SPRINGS HARBOR LAB NY
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The broad goals of my initial proposal were two-fold. First, I proposed the development of a genetic system that would allow complementation screening in animal cells much in the way that this is done in yeast. Second, I proposed the application of this approach to problems of mortality control and tumorigenesis in breast tumor cells and their normal precursors. As a model system, I chose primary, normal human mammary epithelial cells HMEC. Progress over the last year can be summarized as follows 1 Development and validation of the genetic system has been largely completed. 2 We have determined that the lifespan of HMEC cells can be altered by manipulation of telomere length. 3 We have found that a commonly activated cellular oncogene, c-myc, can regulate telomerase activity in HMEC cells and in normal fibroblasts. 4 Either myc expression or telomerase activation can effectively immortalize HMEC cells. 5 We have expanded our genetic analysis of neoplastic transformation to include other aspects of the process, namely resistance to growth inhibitory cytokines.
- Medicine and Medical Research