Appearance of high affinity receptors for type beta transforming growth factor during differentiation of murine...

Recent studies have demonstrated that type beta transforming growth factor (TGF-beta) not only influences cell growth but also affects cell differentiation. In the present study, two different embryonal carcinoma (EC) cell lines and their differentiated cells were examined for the presence of TGF-beta receptors and for their responses to this factor. F9 and PC-13 EC cells bind little, if any, TGF-beta and do not appear to respond to TGF-beta in monolayer or soft agar cultures. Treatment of both EC cell lines with retinoic acid leads to the appearance of irreversibly differentiated cells that begin to exhibit receptors for TGF-beta by 48 h. After an additional 3-5 days, the differentiated cells express approximately 6000 high affinity receptors for TGF-beta, with an apparent dissociation constant of 45 PM. In contrast to the results observed with the parental EC cells, TGF-beta influences the growth of the differentiated cells cultured in both serum-free and serum-containing media. However, TGF-beta, alone or in combination with other growth factors, does not induce the differentiated cells to form colonies in soft agar. The possible relationship of these results to the roles of growth factors during early mammalian development is discussed.