EFFECTS OF HUMAN TROPHOBLAST-INDUCED INTERFERONS ON THE EXPRESSION OFPROTOONCOGENES C-FMS CSF-1R, EGF-R AND C-ERBB2 IN INVASIVE AND NONINVASIVE TROPHOBLAST/

The human cytotrophoblast is the first fetal cell type to arise during embryogenesis and differentiate along two pathways to the invasive (e xtravillous) and non-invasive (villous) populations. The non-invasive villous trophoblast differentiate morphologically and biochemically to form terminally differentiated multinucleated syncytial trophoblast. First trimester invasive and non-invasive trophoblast were isolated fr om human placentae (5-12 weeks) and were cultured in vitro. The villou s trophoblast cells differentiated in vitro to form aggregated syncyti al cells which was associated with increased expression of epidermal g rowth factor receptor (EGF-R). The invasive trophoblast cells expresse d colony-stimulating factor receptor (c-fms/CSF-1R) and c-erbB2 protei ns but low levels of EGF-R. We studied the effects of human trophoblas t-induced interferon (IFN)-alpha/beta on the expression of c-fms/CSF-1 R, EGF-R and c-erbB2 whose ligands are reported to be involved in the regulation of growth and differentiation of normal invasive and non-in vasive trophoblast cells. Human trophoblast-induced IFN-alpha/beta (10 0 IU/ml) reduced the expression of EGF-R in both invasive and non-inva sive trophoblast cells as determined by quantitative enzyme-linked imm unosorbant assay ('ELISA) and western immunoblot methods. The same amo unt of IFN activity reduced the expression of c-fms/CSF-1R and c-erbB2 proto-oncogene products in invasive trophoblast cells. These results may suggest a possible role of trophoblast-induced IFNs in the regulat ion of normal trophoblast growth, differentiation and function. (C) 19 97 W. B. Saunders Company Ltd.