PDGF-LIKE GROWTH FACTORS AND MAMMALIAN EMBRYOGENESIS

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.