The elucidation of the process of cellular proliferation is of fundamental importance in the understanding of a variety of physiological and pathological processes. The most obvious example is in neoplasia, which is associated with fundamental changes in the contro of cell proliferation, although many other examples, from wound healing to atherosclerosis might be cited. Despite many years of intensive investigation the biochemical events involved in cell growth and division are still incompletely understood. Genetic analysis, combined with modern techniques of molecular biology, has allowed the isolation and characterization of a number of critical genes involved in proliferation in yeast. Recently such techniques have been extended to higher eucaryotes and a number of genes complementing temperature sensitive cell cycle mutations have been cloned. This approach allows the identification of previously unknown genes which are critical for cell proliferation. I propose to extend this genetic approach to understanding the cell cycle by developing a novel class of cell proliferation mutants which will not proliferate in a serum-free defined medium containing fibroblast growth factor (FGF) and insulin as the only growth factors. The genes complementing these mutations will then be cloned and the isolated genes and their gene products characterized biochemically. These experiments can identify new genes critical in the cell cycle and thus enhance our understanding of this complex phenomenon. In addition, it will provide a potential shortcut to the cloning of the FGF receptor gene.
| Ittmann, M; Wieczorek, R; Heller, P et al. (1994) Alterations in the p53 and MDM-2 genes are infrequent in clinically localized, stage B prostate adenocarcinomas. Am J Pathol 145:287-93 |
