Expression of the met/Hepatocyte Growth Factor/Scatter Factor Receptor and Its Ligand during Differentiation of Murine P19 Embryonal Carcinoma Cells

Abstract

The met proto-oncogene is a member of the family of tyrosine kinase growth factor receptors and was recently identified as a receptor for hepatocyte growth factor and scatter factor (HGF/SF). From Northern hybridization studies the met/HGF/SF receptor (R) is expressed in many adult and embryonic mouse tissues. To identify which specific differentiated cell types express the met/HGF/SFR and to investigate the biological function of this receptor and its ligand during early murine development, we chose to study the expression of the met/HGF/SFR and HGF/SF during differentiation of the pluripotent P19 murine embryonal carcinoma cell line in culture. In this paper we demonstrate that met/HGF/SFR mRNA, protein, and its ligand are expressed at a low level in undifferentiated P19 cells and that their expression is increased as P19 cells are induced to differentiate into neuroectodermal derivatives following treatment with retinoic acid (RA) and into mesodermal derivatives following treatment with dimethyl sulfoxide (DMSO). From in situ hybridization analyses, only a subpopulation of differentiating P19 cells treated with RA or DMSO expresses high levels of the met /HGF/SFR RNA. In cultures treated with RA and cytosine arabinoside, both met/HGF/SFR mRNA and protein can be localized specifically to nondividing neuronal cells. Expression of the met/HGF/SFR and its ligand, HGF/SF, in undifferentiated P19 cells and differentiated derivatives suggests that stimulation of this signal transduction pathway may be an important event for the control of cell differentiation, proliferation, or positioning during embryogenesis.