Accession Number : ADA336691

Title :   Complementation Screening in Mammalian Cells: Application to Cell Immortalization.

Descriptive Note : Annual rept. 1 Sep 96-31 Aug 97

Corporate Author : COLD SPRING HARBOR LAB OF QUANTITATIVE BIOLOGY NY

Personal Author(s) : Hannon, Gregory J.

PDF Url : ADA336691

Report Date : OCT 1997

Pagination or Media Count : 23

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.

Descriptors :   *NEOPLASMS, *CELLS(BIOLOGY), *MAMMARY GLANDS, *BREAST CANCER, ACTIVATION, BIOLOGY, MAMMALS, HUMANS, ENZYMES, COMPUTER PROGRAMMING, AGING(PHYSIOLOGY), CLINICAL MEDICINE, IN VITRO ANALYSIS, SEQUENCES, IDENTIFICATION, LIMITATIONS, BARRIERS, GENES, ROUTING, ANIMALS, MICE, MEDICAL SERVICES, IN VIVO ANALYSIS, MORTALITY RATE, GENETICS, CULTURES(BIOLOGY), TRANSFORMATIONS, SUPPRESSORS.

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE