Complementation Screening in Mammalian Cells: Application to Cell Immortalization

摘要

The transformation of a normal cell into a cancer cell occurs through a series of genetic and epigenetic alterations that release a cell from controls that restrain its proliferation. The purpose of the research supported by this new investigator award was, broadly, two-fold. The primary goal was to increase our understanding of the transformation process by focusing on one aspect of neoplastic cells, their ability to proliferate indefinitely. The secondary goal which served as a means to the principal end was to develop a vector system that would allow complementation screening in cultured mammalian cells. During the tenure of this award, both goals were largely achieved. We have developed a series of retroviral vectors that allow the introduction of complex libraries into a broad range of cell types. We have validated these vectors for complementation screens and have pursued several findings that are cancer- relevant. Finally, we have taken a step toward understanding the ability of tumor cells to proliferate indefinitely by linking a commonly activated oncogene, c-myc, to the activity of the telomerase enzyme.