The overall aim is to study the role of endogenous growth-promoting peptides, particularly EGF and transforming growth factors (TGF), in mouse embryonal development. TGF-like peptides that are inappropriately expressed have been proposed as normal gene products during embryogenesis in tumor cells. EGF receptors appear as early as 6 1/2 days after fertilization on trophoblast cells; later in gestation nearly all fetal tissues gain the ability to bind EGF. In vitro responses of cells growing on plastic appear to be different from in vivo responses. Cell geometry, cell interactions, and synergisms between stimulating factors may account for the difference. The role of EGF and similar factors will be examined in mouse fetal liver in several different culture systems employing various cell geometries. Responses to EGF and other growth factors including TGF are compared by analyses of growth and production of tissue-specific proteins. The placenta is a rich source of identified factors that support the fetus, as well as of TGFs. Several oncogenes are expressed in the murine and human placenta and other extraembryonal tissues in a stage-specific manner. The role of the oncogenes, c-fos, and c-fms, will be studied by making antibodies to synthetic peptides, by in situ hybridization, and by in vitro translation of mRNA extracted from placenta. An antibody to a synthetic fos peptide has been raised and affinity purified. In immunofluorescence reactions, the antibody reacts with c-fos protein and the intensity of staining correlates well with the abundance of c-fos transcripts in a range of normal murine and human tissues. Teratocarcinoma cell model systems also express c-fos and provide in vitro systems to study the mechanism of its activation. The hypothesis is that oncogene protein products will have a role in growth control or in differentiation/development of fetal or extraembryonal tissues. (M)
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