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Isolation from murine sarcoma cells of novel transforming growth factors potentiated by EGF

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Abstract

Polypeptides classified as transforming growth factors (TGFs) have been found in various neoplastic cells and tumour tissues1–5, and most recently in many non-neoplastic tissues6. These TGFs are low-molecular-weight (7,000–20,000) acid-stable polypeptides, which induce anchorage-dependent non-neoplastic indicator cells to form progressively growing colonies in soft agar. Certain extracellular TGFs isolated from conditioned medium derived from both rodent sarcoma virus-transformed cells and several human tumour cell lines have been shown to compete with epidermal growth factor (EGF) for membrane receptors1,3,4,7. By direct extraction from Moloney sarcoma virus (MSV)-transformed cells, we have isolated two distinct classes of intracellular TGFs, one of which competes with EGF for receptor binding sites, whereas the other does not. We report here that after purification by HPLC, the colony-forming activity of the TGFs that do not compete with EGF for receptor binding was enhanced 100-fold by the addition of EGF. This ability to enhance the growth-stimulating effects of the TGFs is specific to EGF, as insulin, the insulin-like growth factors, platelet-derived growth factor and nerve growth factor do not show this property. In contrast, the colony-forming activity of TGFs that compete with EGF for receptor binding is not potentiated by EGF.

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Authors and Affiliations

  1. Laboratory of Chemoprevention, National Institutes of Health, Bethesda, Maryland, 20205, USA

    A. B. Roberts, M. A. Anzano, L. C. Lamb, J. M. Smith, C. A. Frolik & M. B. Sporn

  2. Laboratory of Viral Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20205, USA

    H. Marquardt & G. J. Todaro

Authors
  1. A. B. Roberts
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  2. M. A. Anzano
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  3. L. C. Lamb
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  4. J. M. Smith
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  5. C. A. Frolik
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  6. H. Marquardt
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  7. G. J. Todaro
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  8. M. B. Sporn
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Roberts, A., Anzano, M., Lamb, L. et al. Isolation from murine sarcoma cells of novel transforming growth factors potentiated by EGF. Nature 295, 417–419 (1982). https://doi.org/10.1038/295417a0

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  • DOI: https://doi.org/10.1038/295417a0

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