Mutant ras promotes haemopoietic cell proliferation or differentiation in a cell-specific manner

The ras gene products play a fundamental role in signal transduction in haemopoiesis. In this study, we have examined the effects of ras upon haemopoietic cell proliferation and differentiation, using two human cell lines which represent different stages of haemopoietic cell maturation. When a mutant H12-ras gene (codon 12: gly-->asp) was expressed in the monoblastic cell line, U937, marked inhibition of growth was seen together with morphological, functional and immunophenotypic evidence of monocytic maturation. Infection of U937 cells with a c-myc retrovirus produced similar changes strongly suggesting that Myc plays an important role in this action of Ras. By contrast, expression of H12-ras promoted factor-independent growth of the multipotent cell line, TF-1. Furthermore, mutant ras dramatically enhanced the growth of TF-1 cells in the presence of added GM-CSF or erythropoietin, but did not influence the state of differentiation of these cells. These data clearly indicate that in haemopoietic cells, Ras may promote either proliferation or differentiation depending upon cell type and/or state of maturation.