Complementation Screening in Mammalian Cells: Application to Cell Immortalization.
Abstract
The defining characteristic of a tumor cell is its ability to proliferate under conditions that prevent the growth of a normal cell. Ultimately, cell proliferation is subject to a genetically programmed limit on the number of divisions that a cell can execute. Studies of human and mouse cells in culture have identified two sequential barriers, M1 (cellular senescence) and M2 (crisis/immortalization), which prevent indefinite division. Circumstantial evidence links the in vitro process of immortalization with the in vivo process of neoplastic transformation. Well characterized tumor suppressor genes must be inactivated as a prerequisite to escape from senescence. Furthermore, escape from crisis is often associated with activation of the telomerase enzyme, a characteristic shared by the majority of human tumors. Conventional routes have failed to generate a basic understanding of the mechanisms which control cellular mortality. This recommends the use of novel approaches to the problem. I have devised a system, based upon recombinant, replication-deficient retroviruses, that allows a genetic approach to biological problems in animal cells. Application of this system individually to the M1 and M2 mortality controls may allow the identification of genes that enforce finite life-span in vitro and prevent transformation in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1997
- Accession Number
- ADA336691
Entities
People
- Gregory Hannon
Organizations
- Cold Spring Harbor Laboratory