Growth-promoting effects of insulin-like growth factor-1 (IGF-1) on hematopoietic cells: overexpression of introduced IGF-1 receptor abrogates interleukin-3 dependency of murine factor-dependent cells by a ligand-dependent mechanism

摘要: Although insulin-like growth factor (IGF-1) stimulated 3H-thymidine incorporation upon addition to the interleukin-3 (IL-3)-dependent cell line FDC-P1, IGF-1 did not relieve IL-3 dependency for growth. To further examine effects of on hematopoietic cells, FDC-P1 cells were infected with a retroviral construct (LISN) containing human receptor (hIGF-1R) and neo genes. IL-3-independent readily isolated after LISN infection when either or supraphysiologic concentrations insulin included in culture medium. These transformed independence by ligand- dependent mechanism because their was presence factors capable supporting autocrine detected. Furthermore, monoclonal antibody (MoAb) directed against IGF-1R (alpha IR-3) inhibited but IL-3-induced proliferation these contained 20- 200- fold more receptors than uninfected cells. In contrast, LISN-infected plated medium without exogenously supplied insulin, factor-independent rarely isolated. Growth also alpha IR-3 MoAb they expressed 100- 400-fold The endogenous and/or present calf serum may have enabled unlike parental would proliferate serum-free defined media again MoAb. results demonstrate that can replace overexpress IGF-1R. Given fairly ubiquitous expression receptor, additional experiments might help determine whether increased lead leukemogenesis tumorigenesis. Moreover, hIGF-1R-infected will be useful investigating mechanisms IGF1-mediated signal transduction are now known response IGF-1.