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Neural and Endocrine Peptides and Receptors pp 407–420Cite as

Physiological Effects of Transforming Growth Factor α

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Abstract

From the conditioned medium of transformed cells, two types of mitogenic polypeptides (α and β) known as transforming growth factors were isolated and characterized. Because of their origin and their abilities to confer phenotypic transformation of cells in culture, much of the studies of transforming growth factors have been focused on their roles in malignancy and their relationship with the oncogenes (for a review, see Brown and Blakeley, 1984; Sporn and Roberts, 1985). However, because of the scarcity of these growth factors from natural sources, little is known about their physiological effects in animals. Recently, our laboratory has synthesized highly purified rat and human transforming growth factor (TGFα). These synthetic materials have been vigorously characterized and found to be indistinguishable from those obtained from the natural source. The availability of these growth factors has made it possible for the first time to study the physiological effects in whole animals. Here, we report our results using the synthetic TGFα.

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References

  • Anzano, M. A., Roberts, A. B., Smith, J. M., Sporn, M. B., and De Larco, J. E., 1983, Sarcoma growth factor from conditioned medium of virally transformed cells is composed of both type α and type β transforming growth factors, Proc. Natl. Acad. Sci. U.S.A. 80:6264–6268.

    Article  PubMed  CAS  Google Scholar 

  • Blomquist, M. C., Hunt, L. T., and Barker, W. C., 1984, Vaccinia virus 19-kilodalton protein: Relationship to several mammalian proteins, including two growth factors, Proc. Natl. Acad. Sci. U.S.A. 81:7363–7367.

    Article  PubMed  CAS  Google Scholar 

  • Brown, J. P., Twardzik, D. R., Marquardt, H., and Todaro, G. J., 1985, Vaccinia virus encodes a polypeptide homologous to epidermal growth factor and transforming growth factor, Nature 313:491–492.

    Article  PubMed  CAS  Google Scholar 

  • Brown, K. D., and Blakeley, D. M., 1984, Transforming growth factors: Sources, properties and possible roles in normal and malignant cell growth control, Biochem. Soc. Trans. 12:168–173.

    PubMed  CAS  Google Scholar 

  • Carpenter, G., and Cohen, S., 1979, Epidermal growth factor, Annu. Rev. Biochem. 48:193–216.

    Article  PubMed  CAS  Google Scholar 

  • Cohen, S., 1962, Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal, J. Biol. Chem. 237:1555–1562.

    PubMed  CAS  Google Scholar 

  • De Larco, J. E., and Todaro, G. J., 1978a, Growth factors from murine sarcoma virus-transformed cells, Proc. Natl. Acad. Sci. U.S.A. 75:4001–4005.

    Article  PubMed  Google Scholar 

  • De Larco, J. E., and Todaro, G. J., 1978b, Epithelioid and fibroblastic rat kidney cell clones: Epidermal growth factor (EGF) receptors and the effect of mouse sarcoma virus transformation, J. Cell. Physiol. 94:335–342.

    Article  PubMed  Google Scholar 

  • Derynck, R., Roberts, A. B., Winkler, M. E., Chen, E. Y., and Goeddel, D. V., 1984, Human transforming growth factor-α: Precursor structure and expression in E. coli, Cell 38:287–297.

    CAS  Google Scholar 

  • Feldman, E. J., Aures, D., and Grossman, M. I., 1978, Epidermal growth factor stimulates ornithine decarboxylase activity in the digestive tract of mouse (40357), Proc. Soc. Exp. Biol. Med. 159:400–402.

    PubMed  CAS  Google Scholar 

  • Gregory, H. 1975, Isolation and structure of urogastrone and its relationship to epidermal growth factor, Nature 257:325–327.

    Article  PubMed  CAS  Google Scholar 

  • Kaplan, P. L, Anderson, M., and Ozanne, B., 1982, Transforming growth factor(s) production enables cells to grow in the absence of serum: An autocrine system, Proc. Natl. Acad. Sci. U.S.A. 79:485–489.

    Article  PubMed  CAS  Google Scholar 

  • Lee, D. C., Rose, T. M., Webb, N. R., and Todaro, G. J., 1985, Cloning and sequence analysis of a cDNA for rat transforming growth factor-α, Nature 313:489–491.

    Article  PubMed  CAS  Google Scholar 

  • Marquardt, H., Hunkapiller, M. W., Hood, L. E., Twardzik, D. R., De Larco, J. E., Stephenson, J. R., and Todaro, G. J., 1983, Transforming growth factors produced by retrovirus-transformed rodent fibroblasts and human melanoma cells: Amino acid sequence homology with epidermal growth factor, Proc. Natl. Acad. Sci. U.S.A. 80:4684–4688.

    Article  PubMed  CAS  Google Scholar 

  • Marquardt, H., Hunkapiller, M. W., Hood, L. E., and Todaro, G. J., 1984, Rat transforming growth factor type 1; structure and relation to epidermal growth factor, Science 223:1079–1081.

    Article  PubMed  CAS  Google Scholar 

  • Massague, J., 1983, Epidermal growth factor-like transforming growth factor, J. Biol. Chem. 258:13606–13612.

    PubMed  CAS  Google Scholar 

  • Moore, G. P. M., Panaretto, B. A., and Robertson, D., 1981, Effects of epidermal growth factor on hair growth in the mouse, J. Endocrinol. 88:293–299.

    Article  PubMed  CAS  Google Scholar 

  • Moses, H. L., Branum, E. L., Proper, J. A., and Robinson, R. A., 1981, Transforming growth factor production by chemically transformed cells, Cancer Res. 41:2842–2848.

    PubMed  CAS  Google Scholar 

  • Murphy, R. A., Rhodes, J. A., Tarn, J., Finke, U., Saunders, M., and Silen, W., 1985, Transforming growth factor (αTGF) inhibits histamine-induced acid secretion in guinea pig gastric mucosa, Fed. Proc. 44:183.

    Google Scholar 

  • Nakhla, A. M., and Tarn, J. P., 1985, Transforming growth factors stimulation of ornithine decarbox-ylase in neonatal mouse tissues, Biochem. Biophys. Res. Comm. 132:1180–1186.

    Article  PubMed  CAS  Google Scholar 

  • Okamoto, S., and Oka, T., 1984, Evidence for physiological function of epidermal growth factor: Pregestational sialoadenectomy of mice decreases milk production and increases offspring mortality during lactation period, Proc. Natl. Acad. Sci. U.S.A. 81:6059–6063.

    Article  PubMed  CAS  Google Scholar 

  • Panaretto, B. A., Moore, G. P. M., and Robertson, D. M., 1982, Plasma concentrations and urinary excretion of mouse epidermal growth factor associated with the inhibition of good consumption and of wool growth in Merino wethers, J. Endocrinol. 94:101–102.

    Article  Google Scholar 

  • Panaretto, B. A., Leish, Z., Moore, G. P. M., and Robertson, D. M., 1984, Inhibition of DNA synthesis in dermal tissue of Merino sheep treated with depilatory doses of mouse epidermal growth factor, J. Endocrinol. 100:25–31.

    Article  PubMed  CAS  Google Scholar 

  • Proper, J. A., Bjornson, C. L., and Moses, H. L., 1982, Mouse embryos contain polypeptide growth factor(s) capable of inducing a reversible neoplastic phenotype in nontransformed cells in culture, J. Cell. Physiol. 110:169–174

    Google Scholar 

  • Reynolds, F. H., Jr., Todaro, G. J., Fryling, C., and Stephenson, J. R., 1981, Human transforming growth factors induce tyrosine phosphorylation of EGF receptors, Nature 292:259.

    Article  PubMed  CAS  Google Scholar 

  • Rhodes, J. A., Tarn, J. P., Finke, U., Saunders, M., Bernanke, J., Silen, W., and Murphy, R. A., 1986, Transforming growth factor alpha (TGFa) inhibits secretion of gastric acid, Proc. Natl. Acad. Sci. U.S.A. 83:3844–3846.

    Article  PubMed  CAS  Google Scholar 

  • Roberts, A. B., Lamb, L. C., Newton, D. L., Sporn, M. B., De Larco, J. E., and Todaro, G. J., 1980, Transforming growth factors: Isolation of polypeptides from virally and chemically transformed cells by acid/ethanol extraction, Proc. Natl. Acad. Sci. U.S.A. 77:3494–3498.

    Article  PubMed  CAS  Google Scholar 

  • Roberts, A. B., Anzano, M. A., Lamb, L. C., Smith, J. M., Frolik, C. A., Marquardt, H., Todaro, G. J., and Sporn, M. B., 1982, Isolation from murine sarcoma cells of novel transforming growth factors potentiated by EGF, Nature 295:417.

    Article  PubMed  CAS  Google Scholar 

  • Sheikh, M. A., and Tarn, J. P., 1985, Total synthesis of biologically-active human transforming growth factor type alpha, in: Proceedings of the Ninth American Peptide Symposium (K. Kopple, C. M. Deber, and V. Hruby, eds.), Pierce Chemical, Rockford, IL, pp. 305–308.

    Google Scholar 

  • Sporn, M. B., and Roberts, A. B., 1985, Autocrine growth factors and cancer, Nature 313:745–747.

    Article  PubMed  CAS  Google Scholar 

  • Sporn, M. B., and Todaro, G. J., 1980, Autocrine secretion and malignant transformation of cells, N. Engl. J. Med. 303:878–880.

    Article  PubMed  CAS  Google Scholar 

  • Stastny, M., and Cohen, S., 1970, Epidermal growth factor IV. The induction of ornithine decarboxylase, Biochim. Biophys. Acta 204:578–589.

    PubMed  CAS  Google Scholar 

  • Tarn, J. P., 1985, Physiological effects of transforming growth factor in the newborn mouse, Science 229:673–675.

    Article  Google Scholar 

  • Tarn, J. P., 1986, Synthesis of alpha transforming growth factor, Methods Enzymol. (in press). Tarn, J. P., Marquardt, H., Rosberger, D. F., Wong, T. W., and Todaro, G. J., 1984, Synthesis of biologically active rat transforming growth factor I, Nature 309:376–378.

    Google Scholar 

  • Todaro, G. J., De Larco, J. E., and Cohen, S., 1976, Transformation by murine and feline sarcoma viruses specifically blocks binding of epidermal growth factor to cells, Nature 264:26–30.

    Article  PubMed  CAS  Google Scholar 

  • Todaro, G. J., Fryling, C., and De Larco, J. E., 1980, Transformation growth factors produced by certain human tumor cells: Polypeptides that interact with epidermal growth factor receptors, Proc. Natl. Acad. Sci. U.S.A. 77:5258–5262.

    Article  PubMed  CAS  Google Scholar 

  • Tucker, R. F., Shipley, G. D., Moses, H. L., and Holley, R. W., 1984, Growth inhibitor from BSC-1 cells closely related to platelet type β transforming growth factor, Science 226:705–707.

    Article  PubMed  CAS  Google Scholar 

  • Twardzik, D. R., Ranchalis, J. E., and Todaro, G. J., 1982a, Mouse embryonic transforming growth factors related to those isolated from tumor cells, Cancer Res. 42:590–593.

    PubMed  CAS  Google Scholar 

  • Twardzik, D. R., Sherwin, S. A., Ranchalis, J. E., and Todaro, G. J., 1982b, Transforming growth factors in the urine of normal, pregnant, and tumor-bearing humans, J. Natl. Cancer Inst. 69:793–798.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. The Rockefeller University, New York, New York, 10021, USA

    James P. Tam

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  1. James P. Tam
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Editors and Affiliations

  1. The George Washington University School of Medicine and Health Sciences, Washington, D.C., USA

    Terry W. Moody

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© 1986 Plenum Press, New York

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Tam, J.P. (1986). Physiological Effects of Transforming Growth Factor α. In: Moody, T.W. (eds) Neural and Endocrine Peptides and Receptors. GWUMC Department of Biochemistry Annual Spring Symposia. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5152-8_27

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  • DOI: https://doi.org/10.1007/978-1-4684-5152-8_27

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5154-2

  • Online ISBN: 978-1-4684-5152-8

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