Abstract
Maximal stimulation of DNA synthesis in quiescent rat mammary (Rama) 27 fibroblasts is elicited by epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF) 18 h after the initial addition of the growth factors-the ‘lag’ period. At maximally-stimulating concentrations, EGF and bFGF are interchangeable 9 h after their initial addition. When the initial concentration of growth factor is below that required to elicit a maximal response, it is possible to increase the level of DNA synthesis by increasing the concentration of growth factor 9 h after its initial addition. When the initial concentration of growth factor is high, substitution by a lower concentration of growth factor after 9 h allows a greater proportion of cells to synthesize DNA than would be expected from a continuous low dose of growth factor. Similar results are obtained when both the growth factor and its concentration are changed 9 h after the initial addition of growth factor. However, when EGF at a low concentration is substituted for a high concentration of EGF or bFGF the resulting increase in the levels of DNA synthesis is greater when EGF rather than bFGF is added for a second time. The half-life of the growth-stimulatory signals delivered by EGF and by bFGF 9 h after their initial addition is 1–2 h. These results suggest that to stimulate DNA synthesis: (i) EGF or bFGF must deliver a signal(s) continuously; (ii) the initial signals produced by EGF and bFGF are equivalent; (iii) the signals produced between 9–18 h by EGF may be different to those produced by bFGF.
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References
Chana, A. K. and Smith, J. A. (1991)Growth Reg. 1:100–104.
Chen, H.-L. (1995) PhD thesis, University of Liverpool, Liverpool, UK.
Escobedo, J. A. and Williams, L. T. (1988)Clinical Res. 36:540.
Fantl, W. J., Johnson, D. E. and Williams, L. T. (1993)Ann. Rev. Biochem. 62:453–481.
Fernig, D. G. and Gallagher, J. T. (1994)Prog. Growth Factor Res. 5:353–377.
Fernig, D. G. Rudland, P. S., and Smith, J. A. (1992)Growth Factors 5:27–39.
Flaumenhaft, R., Moscatelli, D., Saksela, O. and Rifkin, D. B. (1989)J. Cell. Physiol. 140:75–81.
Haugueldemouzon, S., Csermely, P., Zoppini, G. and Kahn, C. R. (1992)J. Cell. Physiol. 150:180–187.
Imamura, T., Engleka, K., Zhan, X., Tokita, Y., Forough, R., Roeder, D., Jackson, A., Maier, J., Hla, T. and Maciag, T. (1990)Science 249:1567–1570.
Imamura, T., Tokita, Y. and Mitsui, Y. (1992)J. Biol. Chem. 267:5676–5679.
Jimenez de Asua, L., O'Farrell, M. K., Clingan, D. and Rudland, P. S. (1977)Proc. Natl. Acad. Sci. 74:3845–3849.
Ke, Y., Wilkinson, M. C., Fernig, D. G., Smith, J. A., Rudland, P. S. and Barraclough, R. (1992)Biochim. Biophys. Acta 1131:307–310.
Mohammadi, M., Dionne, C. A., Li, W., Li, N., Spivak, T., Honegger, A. M., Jaye, M. and Schlessinger, J. (1992)Nature 358:681–684.
Otto, A. M., Ulrich, M.-O. and Jimenez de Asua, L. J. (1981)J. Cell. Physiol. 108:145–153.
Peters, K. G., Marie, J., Wilson, E., Ives, H. E., Escobedo, J., Delrosario, M., Mirada, D. and Williams, L. T. (1992)Nature 358:678–681.
Pledger, W. J., Stiles, C. D., Antoniades, H. N. and Scher, C. D. (1978)Proc Natl Acad Sci USA 75:2839–2843.
Pouyssegur, J. and Seuwen, K. (1992)Ann. Rev. Physiol. 54:195–210.
Presta, M., Maier, J. A. M., Rusnati, M. and Ragnotti, G. (1989)J. Cell. Physiol. 140:68–74.
Presta, M., Tiberio, L., Rusnati, M., Dellera, P. and Ragnotti, G. (1991)Cell Regul. 2:719–726.
Reid, T. W. and Reid, W. A. (1987)J. Biol. Chem. 262:229–233.
Richmond, K. M. V., Kubler, A.-M., Martin, F. and Jimenez de Asua, L. (1980)J. Cell. Physiol. 103:77–85.
Roberts, T. M. (1992)Nature 360:534–535.
Rudland, P. S. and Jimenez de Asua, L. (1979)Biochim. Biophys. Acta 560:91–133.
Rudland, P. S., Seifert, W. and Gospodarowicz, D. (1974)Proc. Natl. Acad. Sci. 71:2600.
Rudland, P. S., Twiston Davis, A. C. and Tsao, S. W. (1984)J. Cell. Physiol. 120:364–376.
Shechter, Y., Hernaez, L. and Cuatrecasas, P. (1978)Proc. Natl. Acad. Sci. 75:5788–5791.
Smith, J. A., Ham, J., Winslow, D. P., O'Hare, M. J. and Rudland, P. S. (1984)J. Chromatogr. 305:295–308.
White, M. F., and Kahn, C. R. (1994)J. Biol. Chem. 269:1–4.
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Chen, HL., Rudland, P.S., Smith, J.A. et al. Late signals are required for the stimulation of DNA synthesis in rat mammary fibroblasts by growth factors. Biosci Rep 16, 249–263 (1996). https://doi.org/10.1007/BF01207339
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DOI: https://doi.org/10.1007/BF01207339