Mouse embryos contain polypeptide growth factor(s) capable of inducing a reversible neoplastic phenotype in nontransformed cells in culture

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Abstract
A growth‐factor‐like substance capable of inducing nontransformed mouse AKR‐2B, rat NRK, and EGF‐receptorless mouse NR6 cells to form progressively growing colonies in soft agar was identified in acid/ethanol extracts of 17‐day mouse embryos. This “mouse embryo factor” (MEF) is similar to previously described transforming growth factors in that it is capable of stimulating DNA synthesis and conferring a reversible transformed morphology on nontransformed cells in vitro. Passage of crude embryo extracts over a Bio‐Gel P‐60 column gave a major peak of soft agar growth‐stimulating activity in the 15,000 molecular weight range with a minor peak at about 22,000. This biological activity was sensitive to treatment with either trypsin or dithiothreitol, but was unaffected by heat (56°C for 30 minutes or 100°C for 3 minutes), indicating that the activity is due to a heat‐stable polypeptide(s) with disulfide bonds. Separation of these polypeptide(s) by chromatography on carboxymethyl cellulose revealed two peaks of soft agar growth‐stimulating activity which did not cochromatograph with a peak of epidermal growth factor receptor‐competing activity. The similarities of this mouse embryo‐derived growth factor to previously identified transforming growth factors suggest that both fetal development and neoplastic transformation may be affected by similar mechanisms.