Effects of human trophoblast-induced interferons on the expression of proto-oncogenes c-fms/CSF-1R, EGF-R and c-erbB2 in invasive and non-invasive trophoblast.
The human cytotrophoblast is the first fetal cell type to arise during embryogenesis and differentiate along two pathways to the invasive (extravillous) 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 from human placentae (5-12 weeks) and were cultured in vitro. The villous trophoblast cells differentiated in vitro to form aggregated syncytial cells which was associated with increased expression of epidermal growth factor receptor (EGF-R). The invasive trophoblast cells expressed colony-stimulating factor receptor (c-fms/CSF-1R) and c-erbB2 proteins but low levels of EGF-R. We studied the effects of human trophoblast-induced interferon (IFN)-alpha/beta on the expression of c-fms/CSF-1R, EGF-R and c-erbB2 whose ligands are reported to be involved in the regulation of growth and differentiation of normal invasive and non-invasive trophoblast cells. Human trophoblast-induced IFN-alpha/beta (100 IU/ml) reduced the expression of EGF-R in both invasive and non-invasive trophoblast cells as determined by quantitative enzyme-linked immunosorbant assay ('ELISA') and western immunoblot methods. The same amount 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 regulation of normal trophoblast growth, differentiation and function.
Aboagye-Mathiesen
G
G
Department of Virus and Cancer, Danish Cancer Society, The Science Park, Denmark.
Zdravkovic
M
M
Tóth
F D
FD
Ebbesen
P
P
D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000302:isolation & purification / Q000494:pharmacology*; D016899:Interferon-beta / Q000302:isolation & purification / Q000494:pharmacology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D016184:Receptors, Colony-Stimulating Factor / Q000096:biosynthesis; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
D066246:ErbB Receptors; D016898:Interferon-alpha; D016899:Interferon-beta; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; D016184:Receptors, Colony-Stimulating Factor; C000715470:MAS1 protein, human