EGF promotes development of a differentiated trophoblast phenotype having c-myc and junB proto-oncogene activation

Human placental cytotrophoblast cells differentiate by a process of fusion into a syncytium. This process is stimulated by EGF but also occurs spontan eously at a slower rate in cultured cytotrophoblast cells. To determine nuc lear proto-oncogene changes mediating these events, c-myc, c-fos, c-jun and junB were measured in spontaneously differentiating cells and in cells exp osed to EGF. c-myc showed a transient rise in expression at 4-8 h with augm ented expression by EGF, occurring even in the absence of serum or attachme nt, c-myc and c-jun declined during culture, but c-fos and particularly jun B show-ed increased expression by day 3 with marked responses to EGF stimul ation. Syncytia induced to form by EGF exposure for 18 h demonstrated marke d junB expression after rechallenge with 40 min EGF exposure, but negligibl e responses of c-fos and c-jun. c-myc showed increased expression after 6 h EGF exposure throughout the culture period and in syncytia. The results in dicate EGF promotes a syncytial phenotype characterized by c-fos and junB e xpression during syncytial formation. EGF continues to elicit junB and c-my c responsiveness in more mature syncytium, indicative of continued EGF acti ons which mag include acting as a survival factor, as an hCG secretagogue, and as an inducer of continued development of the syncytium. (C) 1999 W. B. Saunders Company Ltd.