The goal of this project is to characterize the molecular mechanisms of cell growth control in T cells, and to identify the defects in the leukemia/ lymphoma cells. The structure and function of mouse IL-2 induced genes will be characterized by Northern blot analysis or DNA sequencing. The promoter binding factor which must be activated by IL-2 will be isolated and characterized by gel shift assay. The role of these genes and their products in the regulation of T cell proliferation will be elucidated using antibodies or antisense oligonucleotides. In addition, metabolic inhibitors which arrest cells at various phases of the cell cycle will be used to characterize normal human T cells and identify the defects in leukemia/lymphoma cells. Normal cells and leukemia/ lymphoma cells will be characterized using MTT or propidium iodide. The differences among proteins in the arrested cells of both types will be characterized by chemicals on two dimensional gel electrophoresis. The different proteins will be further characterized. Molecular constructs joining toxin genes with promoters of the genes abnormally activated in leukemia/lymphoma cells will be developed. This will allow the prevention of growth of the leukemia/lymphoma cells efficiently and selectively in vitro. This project may provide new insights into the regulatory mechanisms of T cell proliferation, and enhance understanding of the defects seen in the regulation of a variety of leukemia/lymphoma cells. It may yield new ideas regarding the development of rational therapeutic approaches in patients.
| Yamamoto, M; Yoshida, M; Ono, K et al. (1994) Effect of tumor suppressors on cell cycle-regulatory genes: RB suppresses p34cdc2 expression and normal p53 suppresses cyclin A expression. Exp Cell Res 210:94-101 |
| Yoshida, M; Yamamoto, M; Nikaido, T (1992) Quercetin arrests human leukemic T-cells in late G1 phase of the cell cycle. Cancer Res 52:6676-81 |
