Summary
We have previously shown that differentiation of embryonal carcinoma (EC) cells leads to both increased binding of FGF (fibroblast growth factor) and suppression of k-FGF expression. In the current study, we examined the expression of FGF receptors by EC cells, EC-derived differentiated cells and early mammalian embryos using the technique of reverse transcription-polymerase chain reaction (RT-PCR). We determined that both mouse, F9, and human, NT2/D1, EC cells as well as their differentiated counterparts express transcripts for two forms of FGF receptors, bek (bacterially expressed kinase) and flg (fms-like gene). In addition, we determined that mouse blastocysts express flg transcripts. The presence of FGF receptor transcripts in early embryos and the previous finding of FGF-related activity in medium conditioned by mouse blastocysts argue that the FGF family plays important roles during early mammalian development.
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References
Amaya, E.; Musci, T. J.; Kirschner, M. W. Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in xenopus embryos. Cell 66:257–270; 1991.
Baird, A.; Klagsburn, M. The fibroblast growth factor family. Cancer Cells 3:239–242; 1991.
Braunhut, S. J.; Gudas, L. J.; Kurokawa, T., et al. Expression of fibroblast growth factor by F9 teratocarcinoma cells as a function of differentiation. J. Cell Biol. 108:2467–2476; 1989.
Burrus, L. W.; Zuber, M. Z.; Lueddecke, B., et al. Characterization of a non-tyrosine kinase FGF-binding protein. In: Attle, A. D., ed. Molecular biology of atherosclerosis. New York: Elsevier Science Publishing Co., Inc.; 1990:225–234.
Campbell, W. J.; Kelly, D.; Rizzino, A. Expression of transforming growth factor-β3 by embryonal carcinoma cells, parietal endoderm-like cells and early mouse embryos. In Vitro Cell. Dev. Biol. 26:1181–1185; 1990.
Dionne, C. A.; Crumley, G.; Bellot, F., et al. Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors. EMBO J. 9:2692; 1990.
Fasel, N. J.; Bernard, M.; Deglon, N., et al. Isolation from mouse fibroblasts of a cDNA encoding a new form of the fibroblast growth factor receptor (flg). Biochem. Biophys. Res. Comm. 178:8–15; 1991.
Hattori, Y.; Odagiri, H.; Nakatani, H., et al. K-sam, an amplified gene in stomach cancer, is a member of the heparin-binding growth factor receptor genes. Proc. Natl. Acad. Sci. USA 87:5983–5987; 1990.
Haub, O.; Goldfarb, M. Expression of the fibroblast growth factor-5 gene in the mouse embryo. Devel. 112:397–406; 1991.
Hébert, J. M.; Basilico, C.; Goldfarb, M., et al. Isolation of cDNAs encoding four mouse FGF family members and characterization of their expression patterns during embryogenesis. Devel. Biol. 138:454–463; 1990.
Hébert, J. M.; Boyle, M.; Martin, G. R. mRNA localization studies suggest that murine FGF-5 plays a role in gastrulation. Development 112:407–415; 1991.
Hou, J.; Kan, M; McKeehan, K., et al. Fibroblast growth factor receptors from liver vary in three structural domains. Science 251:665–668; 1991.
Houssaint, E.; Blanquet, P. R.; Champion-Arnaud, P., et al. Related fibroblast growth factor receptor genes exist in the human genome. Proc. Natl. Acad. Sci. USA 87:8180–8184; 1990.
Jakobovits, A.; Shackleford, G. M.; Varmus, H. E., et al. Two protooncogenes implicated in mammary carcinogenesis, int-1 and int-2, are independently regulated during mouse development. Proc. Natl. Acad. Sci. USA 83:7806–7810; 1986.
Keegan, K.; Johnson, D. E.; Williams, L. T., et al. Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3. Proc. Natl. Acad. Sci. USA 88:1095–1099; 1991.
Kelly, D.; Campbell, W. J.; Tiesman, J., et al. Regulation and expression of transforming growth factor type-β during early mammalian development. Cytotechnology 4:227–242; 1990.
Kiefer, M. C.; Stephans, J. C.; Crawford, K., et al. Ligand-affinity cloning and structure of a cell surface heparan sulfate proteoglycan that binds basic fibroblast growth factor. Proc. Natl. Acad. Sci. USA 87:6985–6989; 1990.
Kornbluth, S.; Paulson, K. E.; Hanafusa, H. Novel tyrosine kinase identified by phosphotyrosine antibody screening of cDNA libraries. Molecular and Cellular Biology 8:5541–5544; 1988.
Lee, P. L.; Johnson, D. E.; Cousens, L. S., et al. Purification and complementary DNA cloning of a receptor for basic fibroblast growth factor. Science 245:57–60; 1989.
Mansukhani, A.; Moscatelli, D.; Talarico, D., et al. A murine fibroblast growth factor (FGF) receptor expressed in CHO cells is activated by basic FGF and kaposi FGF. Proc. Natl. Acad. Sci. USA 87:4378–4382; 1990.
Miki, T.; Fleming, T. P.; Bottaro, D. P., et al. Expression cDNA cloning of the KGF receptor by creation of a transforming autocrine loop. Science 251:7275; 1991.
Partanen, J.; Mäkelä, T. P.; Eerola, E., et al. FGFR-4, a novel acidic fibroblast growth factor receptor with a distinct expression pattern. Embo. J. 10:1347–1354; 1991.
Peters, G.; Brookes, S.; Smith, R., et al. The mouse homolog of the hst/k-FGF gene is adjacent to int-2 and is activated by proviral insertion in some virally induced mammary tumors. Proc. Natl. Acad. Sci. USA 86:5678–5682; 1989.
Rappolee, D. A.; Sturm, K. S.; Schultz, G. A., et al. The expression of growth factor ligands and receptors in preimplantation mouse embryos. In: Heyner, S.; Wiley, L., eds. Early embryo development and paracrine relationships. New York, NY: Wiley Liss; 1990:11–25.
Reid, H. H.; Wilks, A. F.; Bernard, O. Two forms of the basic fibroblast growth factor receptor-like mRNA are expressed in the developing mouse brain. Proc. Natl. Acad. Sci. USA 87:1596–1600; 1990.
Rizzino, A. Early mouse embryos produce and release factors with transforming growth factor activity. In Vitro Cell. Dev. Biol. 21:531–536; 1985.
Rizzino, A. Use of embryonal carcinoma cells to study growth factors during early mammalian development. In: Rosenblum, I. Y.; Heyner, S., eds. Growth factors in mammalian development. Boca Raton, FL: CRC Press, Inc.; 1989:113–134.
Rizzino, A.; Kuszynski, C.; Ruff, E., et al. Production and utilization of growth factors related to fibroblast growth factor by embryonal carcinoma cells and their differentiated cells. Developmental Biol. 129:61–71; 1988.
Rizzino, A.; Orme, L.; De Larco, J. E. Embryonal carcinoma cell growth and differentiation: production of and response to molecules with transforming growth factor activity. Exp. Cell. Res. 143:143–152; 1983.
Rizzino, A.; Tiesman, J.; Hines, R., et al. Developmental regulation of the KS-FGF oncogene by embryonal carcinoma cells and early mouse embryos. In: Heyner, S.; Wiley, L., eds. Early development and paracrine relationships. UCLA Symposia Proceedings; 1990:53–66.
Ruta, M.; Howk, R.; Ricca, G. et al. A novel protein tyrosine kinase gene whose expression is modulated during endothelial cell differentiation. Oncogene 3:9–15; 1988.
Safran, A.; Avivi, A.; Orr-Urtereger, A., et al. The murineflg gene encodes a receptor for fibroblast growth factor. Oncogene 5:635–643; 1990.
Slack, J. M.; Darlington, W.; Heath, B. G., et al. Mesoderm induction in early Xenopus embryos by heparin-binding growth factors. Nature 326:197–200; 1987.
Tiesman, J.; Rizzino, A. Expression and developmental regulation of the k-FGF oncogene in human and murine embryonal carcinoma cells. In Vitro Cell. Dev. Biol. 25:1193–1198; 1989.
Velcich, A.; Delli-Bovi, P.; Mansukhani, A., et al. Expression of the K-fgf protooncogene is repressed during differentiation of F9 cells. Oncogene Res. 5:31–37; 1989.
Yoshida, T.; Muramatsu, H.; Muramatsu, T., et al. Differential expression of two homologous and clustered oncogenes, Hst1 and Int-2, during differentiation of F9 cells. Biochem. Biophys. Res. Comm. 157:618–625; 1988.
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Campbell, W.J., Miller, K.A., Anderson, T.M. et al. Expression of fibroblast growth factor receptors by embryonal carcinoma cells and early mouse embryos. In Vitro Cell Dev Biol - Animal 28, 61–66 (1992). https://doi.org/10.1007/BF02631080
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DOI: https://doi.org/10.1007/BF02631080