EGF induces differentiation of an IL-3-dependent cell line expressing the EGF receptor

Interleukin 3 (IL-3) is a T cell-derived lymphokine that supports the growth and development of hematopoietic cells. Tyrosine phosphorylation has been suggested to play an important role in IL-3-dependent cell proliferation. To test whether a growth factor receptor carrying a tyrosine kinase can be functional in IL-3 dependent cells, we used a retroviral vector to introduce the human EGF receptor into a murine IL-3-dependent pre-mast cell line, IC2. The EGF receptors expressed on the infected clones bind EGF with both high and low affinities. EGF stimulates the infected cells for a short term growth response. In the presence of IL-3 and EGF, infected clones differentiate into more mature mast cells characterized by increases in intracellular granulation and histamine content. This differentiation is reversible when EGF is removed. EGF induces tyrosine phosphorylation of several cellular proteins and the expression of oncogenes c-fos and c-myc, in a manner analogous to IL-3 stimulation. These results indicate that the EGF receptor is functional in the pre-mast IC2 cells; EGF can support short-term proliferation and activates the signals that induce cell differentiation. Thus, EGF receptor-expressing IC2 cells provide a unique cellular system for in vitro study of mast cell differentiation.