Embryonal carcinoma (EC) cells, which represent a useful model system for studying early mammalian development, can be used to probe the role of growth factors during embryogenesis. Recent studies have established that EC cells release at least two endogenous growth factor activities: One that behaves as a transforming growth factor (TGF) but differs from the two TGFs that have been purified thus far, and a second that is similar to platelet-derived growth factor (PDGF). Further study of these factors has shown that: 1) early mouse embryos also release a TGF-like activity, 2) production of both the PDGF-like activity and the TGF-like activity decreases after EC cells differentiate, 3) human PDGF can stimulate the growth of differentiated cells derived from EC cells and early mouse embryos, and 4) human PDGF exhibits TG activity. These findings suggest that the PDGF-like and TGF-like activities are related and play a role in growth control during early mammalian development. The importance of these findings is highlighted by recent reports that the amino acid sequence of PDGF and the gene product of the oncogene v-sis are strikingly similar. To better understand the functions of the factors released by EC cells, the following studies are proposed: 1) purify and characterize the PDGF-like and TGF-like activities released by EC cells and determine whether one factor is responsible for both activities, 2) examine the biological properties of the purified factor(s), in particular determine whether the purified factor(s) stimulates the growth of specific early embryonic cells, 3) determine whether a gene that is closely related to the oncogene sis is expressed in EC cells but repressed in their differentiated cells, and 4) determine whether the responses to particular growth factors by EC-derived endoderm-like cells are modulated by other growth factors. It is anticipated that the proposed work will provide important insights into the functions of endogenous growth factors released by early embryonic cells and provide the groundwork for a future goal, namely, to isolate and study the gene that codes for the PDGF-like factor.
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