Abstract
Transforming growth factor-α (TGF-α) is a polypeptide which is structurally related to epidermal growth factor (EGF)1,2 and binds to the EGF receptor3,4. TGF-α synthesis occurs in a variety of neoplastic cells5 and during early fetal development6,7 but has not been reported in normal cells of the adult organisms. TGF-α has therefore been regarded as an embryonic growth factor which is inappropriately expressed during neoplasia. Here we report that primary cultures of normal human keratinocytes synthesize TGF-α. Furthermore, we show that addition of EGF or TGF-α to these cultures induces TGF-α gene expression, suggesting that a mechanism of auto-induction exists. Analysis of normal skin biopsies using in situ hybridization and immunohistochemistry demonstrates the in vivo presence of TGF-α messenger RNA and protein in the stratified epidermis.
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References
1. Marquardt, H., Hunkapiller, M. W., Hood, L. E. & Todaro, G. J. Science 223, 1079–1082 (1984). 2. Derynck, R., Roberts, A. B., Winkler, M. E., Chen, E.–Y. & Goeddel, D. V. Cell 38, 287–297 (1984). 3. Todaro, G. J., Fryling, C. & De Larco, J. E. Proc. natn. Acad. Sci. U.S.A. 77,5258–5262 (1980). 4. Massague, J. J. biol. Chem. 258, 13614–13620 (1983). 5. Derynck, R. et al. Cancer Res. 47, 707–712 (1987). 6. Lee, D. C., Rochford, R. M., Todaro, G. J. & Villareal, L. P. Molec. cell. Biol. 5, 3644–3646 (1985). 7. Twardzik, D. R. Cancer Res. 45, 5413–5416 (1985). 8. De Larco, J. E. & Todaro, G. J. Proc. natn. Acad. Sci. U.S.A. 75, 4001–4005 (1978). 9. Samsoondar, J., Kobrin, M. S. & Kudlow, J. E. J. biol. Chem. 261, 14408–14413 (1986). 10. Sporn, M. B. & Todaro, G. J. New Engl. J. Med. 303, 878–880 (1980). 11. Rosenthal, A., Lindquist, P. B., Bringman, T. S., Goeddel, D. V. & Derynck, R. Cell 46, 301–309 (1986). 12. Wille, J. J., Pittelkow, M. R., Shipley, G. D. & Scott, R. E. J. cell. Physiol. 121, 31–44 (1984). 13. Eisinger, M. & Marko, O. Proc. natn. Acad. Sci. U.S.A. 79, 2018–2022 (1982). 14. Coffey, R. J., Shipley, G. D. & Moses, H. L. Cancer Res. 46, 1164–1169 (1986). 15. Coffey, R. J. et al. Cancer Res. (in the press). 16. Derynck, R. in Oncogenes, Genes and Growth Factors (ed. Guroff, G.) 133–163 (Wiley, New York, 1987). 17. Bringman, T. S., Lindquist, P. B. & Derynck, R. Cell 48, 429–440 (1987). 18. Rheinwald, J. G. & Green, H. Nature 265, 421–424 (1977). 19. O'Keefe, E., Battin, T. & Payne, R. /. invest. Derm. 78, 482–487 (1982). 20. Nanney, L. B., McKanna, J. A., Stoscheck, C. M., Carpenter, G. & King, L. E. J. invest. Derm. 82, 165–169 (1984). 21. Leof, E. B. et al. Proc. natn. Acad. Sci. U.S.A. 83, 2453–2457 (1986). 22. Zullo, J. N., Cochran, B. N., Huang, A. S. & Stiles, C. D. Cell 43, 793–800 (1985). 23. Shipley, G. P., Pittelkow, M. R., Wille, J. J. Jr, Scott, R. E. & Moses, H. L. Cancer Res. 46, 2068–2971 (1986). 24. Oka, Y. & Orth, D. N. J. din. Invest. 72, 249–259 (1983). 25. Weinstein, G. D., McCullough, J. L. & Ross, P. A. J. invest. Derm. 85, 579–583 (1985). 26. Nanney, L. B., Stoscheck, C. M., Magid, M. & King, L. E. J. invest. Derm. 86,260–265 (1986). 27. Schwab, M., Alitalo, K., Varmus, H. E. & Bishop, J. M. Nature 303, 497–501 (1983). 28. Dobner, P. R., Kawasaki, E. S., Yu, L.–Y. & Bancroft, F. C. Proc. natn. Acad. Sci. U.S.A. 78,2230–2234 (1981). 29. Thomas, P. S. Proc. natn. Acad. Sci. U.S.A. 77, 5201–5205 (1980). 30. Melton, D. A. et al. Nucleic Acids Res. 12, 7035–7056 (1984). 31. Mason, A. J. et al. Science 234, 1372–1378 (1986).
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Coffey, R., Derynck, R., Wilcox, J. et al. Production and auto-induction of transforming growth factor-α in human keratinocytes. Nature 328, 817–820 (1987). https://doi.org/10.1038/328817a0
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DOI: https://doi.org/10.1038/328817a0
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