Developmentally regulated expression of insulin-like growth factors by differentiated murine teratocarcinomas and extraembryonic mesoderm.
The expression of plasma membrane receptors for insulin-like growth factors (IGFs) by PC13 embryonal carcinoma (EC) cells, and their immediate differentiated progeny PC13END was examined by binding radiolabelled IGF-I to cell monolayers. Both cell types express high-affinity IGF receptors, but the apparent number of unoccupied receptors sites falls by about 60% upon differentiation. Crosslinking studies reveal that both type 1 and type 2 IGF receptors are expressed by PC13EC cells. PC13END-cell-conditioned medium contains developmentally regulated, separable activities, one of which reacts directly with IGF-II, and the other with IGF for plasma membrane receptors. The former activity represents a soluble secreted IGF-binding protein. The latter activity is structurally and functionally similar to rat IGF-II. Polyclonal antibodies raised against purified rat IGF-II specifically recognize multiple forms of IGF in radiolabelled culture supernatants and material which closely resembles the soluble IGF-binding protein. Immunoprecipitation of radiolabelled culture supernatants with anti-rat IGF-II reveals that the differentiation of PC13EC cells is accompanied by the coexpression of IGF-like molecules and the soluble binding protein, and that IGF-like molecules are expressed by extraembryonic tissues of mesodermal origin in the early postimplantation mouse embryo. These findings show that IGF-like molecules are expressed in early mammalian development and may act in an autocrine fashion in vivo.
D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D054278:Embryonal Carcinoma Stem Cells; D007158:Immunologic Techniques; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000276:immunology; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000276:immunology; D014411:Neoplastic Stem Cells / Q000166:cytology*; D011972:Receptor, Insulin / Q000276:immunology / Q000378:metabolism; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000096:biosynthesis*; D013724:Teratoma / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology
D017451:Receptors, Somatomedin; D013002:Somatomedins; D014212:Tretinoin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011972:Receptor, Insulin