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Biological effects of transforming growth factors

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Advances in Growth Hormone and Growth Factor Research

Abstract

Transforming growth factors (TGFs) were originally defined by their biological effects on fibroblastic cells (for review see Goustin et al. 1986). These effects included induction of morphological transformation in monolayer culture and Stimulation of colony formation in soft agar. While the early studies with TGFα were somewhat misleading with respect to the function of these factors, they did lead to the purification and cloning of two important growth-regulatory molecules, TGFα and TGFβ. Interestingly, one of these factors (TGFα) is a potent mitogen for a wide variety of cell types, while the other (TGFβ) is the most potent growth-inhibitory Polypeptide known for most cell types (Goustin et al. 1986).

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References

  • Anzano MA, Roberts AB, Smith JM, Sporn MB, DeLarco JE (1983) Sarcoma growth factor from conditioned medium of virally transformed cells is composed of both type-alpha and type-beta transforming growth factors. Proc Natl Acad Sci USA 80: 6264–6268

    Article  PubMed  CAS  Google Scholar 

  • Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB (1983) Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem 258:7155–7160

    PubMed  CAS  Google Scholar 

  • Cate RL, Mattaliano RJ, Hession C, Tizard R, Farber NM, Cheung A, Ninfa EG, Frey AZ, Gash DJ, Chow EP, Fisher A, Bertonis JM, Torres G, Wallner BP, Ramachandran KL, Ragin RC, Managanaro TF, MacLaughlin DT, Donahoe PK (1986) Isolation of the bovine and human genes for Müllerian inhibiting substance and expression of the human gene in animal cells. Cells 45: 685–698

    Article  CAS  Google Scholar 

  • Cheifetz S, Weatherbee JA, Tsang ML-S, Anderson JK, Mole JE, Lucas R, Massague J (1987) The transforming growth factor-beta system, a complex pattern of cross-reactive ligands and receptors. Cells 48: 409–415

    Article  CAS  Google Scholar 

  • Childs CB, Proper JA, Tucker RF, Moses HL (1982) Serum contains platelet-derived transforming growth factor. Proc Natl Acad Sci USA 79: 5312–5316

    Article  PubMed  CAS  Google Scholar 

  • Coffey RJ, Derynck R, Wilcox JN, Bringman TS, Goustin S, Moses HL, Pittelkow MR (1987) Production and auto-induction of transforming growth factor-beta in human keratinocytes. Nature 328:817–820

    Article  PubMed  CAS  Google Scholar 

  • Coughlin JP, Donahoe PK, Budzik GP, MacLaughlin DT (1987) Müllerian inhibiting substance blocks autophosphorylation of the EGF receptor by inhibiting tyrosine kinase. Mol Cell Endocrinol 49: 75–86

    Article  PubMed  CAS  Google Scholar 

  • DeLarco JE, Todaro GJ (1978) Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci USA 75: 4001–4005

    Article  CAS  Google Scholar 

  • Derynck R (1986) Transforming growth factor-alpha: structure and biological activities. J Cell Biochem 32: 293–304

    Article  PubMed  CAS  Google Scholar 

  • Derynck R, Jarrett JA, Chen EY, Eaton DH, Bell JR, Assoian RK, Roberts AB, Sporn MB, Goeddel DV (1985) Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature 316:701–705

    Article  PubMed  CAS  Google Scholar 

  • Derynck R, Jarrett JA, Chen EY, Goeddel DV (1986) The murine transforming growth factor-beta precursor. J Biol Chem 261:4377–4379

    PubMed  CAS  Google Scholar 

  • Edwards DR, Murphy G, Reynolds JJ, Whitham SE, Docherty JP, Angel P, Heath JK (1987) Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor. EMBO J 6: 1899–1904

    PubMed  CAS  Google Scholar 

  • Fernandez-Pol JA, Talked VD, Klos DJ, Hamilton PD (1987) Suppression of the EGF-dependent induction of c-mycproto-oncogene expression by transforming growth factor-beta in a human breast carcinoma cell line. Biochem Biophys Res Commun 144:1197–1205

    Article  PubMed  CAS  Google Scholar 

  • Frolik CA, Wakefield LM, Smith DM, Sporn MB (1984) Characterization of a membrane receptor for transforming growth factor-beta in normal rat kidney fibroblasts. J Biol Chem 259:10995–11000

    PubMed  CAS  Google Scholar 

  • Gentry LE, Webb NR, Lim GJ, Brunner AM, Ranchalis JE, Twardzik DR, Lioubin MN, Marquardt H, Purchio AF (1987) Type-1 transforming growth factor-beta: amplified expression and secretion of mature and precursor Polypeptides in Chinese hamster ovary cells. Mol Cell Biol 7: 4318–4327

    Google Scholar 

  • Goustin AS, Leof EB, Shipley GD, Moses HL (1986) Perspective in cancer research: growth factors and cancer. Cancer Res 46:1015–1029

    PubMed  CAS  Google Scholar 

  • Holley RW, Armour R, Baldwin JH (1978) Density-dependent regulation of growth of BSC-1 cells in cell culture: growth inhibitors formed by the cells. Proc Natl Acad Sci USA 75: 1864–1866

    Article  PubMed  CAS  Google Scholar 

  • Ignotz RA, Massague J (1986) Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem 261:4337–4345

    PubMed  CAS  Google Scholar 

  • Ignotz RA, Endo R, Massague J (1987) Regulation of fibronectin and type-I collagen mRNA levels by transforming growth factor-beta. J Biol Chem 262:6443–6446

    PubMed  CAS  Google Scholar 

  • Keski-Oja J, Lyons RM, Moses HL (1987) Immunodetection and modulation of cellular growth with antibodies against native transforming growth factor-beta. Cancer Res 47: 6451–6458

    PubMed  CAS  Google Scholar 

  • Laiho M, Saksela O, Andreasen PA, Keski-Oja J (1986) Enhanced production and extracellular deposition of the endothelial-type Plasminogen activator inhibitor in cultured human lung fibroblasts by transforming growth factor-beta. J Cell Biol 103:2403–2410

    Article  PubMed  CAS  Google Scholar 

  • Lawrence DA, Pircher R, Kryceve-Martinerie C, Jullien P (1984) Normal embryo fibroblasts release trasforming growth factors in a latent form. J Cell Physiol 121: 184–188

    Article  PubMed  CAS  Google Scholar 

  • Leof EB, Proper JA, Goustin AS, Shipley GD, DiCorleto E, Moses HL (1986) Induction of c-sismRNA and activity similar to platelet-derived growth factor by transforming growth factor-beta: a proposed model for indirect mitogenesis involving autocrine activity. Proc Natl Acad Sci USA 83:2453–2457

    Article  PubMed  CAS  Google Scholar 

  • Like B, Massague J (1986) The antiproliferative effect of type beta transforming growth factor occurs at a level distal from receptors for growth-activating factors. J Biol Chem 261:13426–13429

    PubMed  CAS  Google Scholar 

  • Marquardt H, Hunkapiller MW, Hood LE, Todaro GJ (1984) Rat transforming growth factor type 1: structure and relation to epidermal growth factor. Science 223:1079–1082

    Article  PubMed  CAS  Google Scholar 

  • Mason AJ, Hayflick JS, Ling N, Esch F, Ueno N, Ying Y, Guillemin R, Niall H, Seeburg PH (1985) Complementary DNA sequences of ovarian follicular fluid inhibin show precursor structure and homology with transforming growth factor-beta. Nature 318:659–663

    Article  PubMed  CAS  Google Scholar 

  • Massague J (1985) Subunit structure of a high-affinity receptor for type-beta transforming growth factor. Evidence for a disulfide-linked glycosylated receptor complex. J Biol Chem 260: 7059–7066

    PubMed  CAS  Google Scholar 

  • Massague J (1987) The TGF-beta family of growth and differentiation factors. Cell 49:437–438

    Article  PubMed  CAS  Google Scholar 

  • Massague J, Like B (1985) Cellular receptors for type-beta transforming growth factor. Ligand binding and affinity labeling in human and rodent cell lines. J Biol Chem 260: 2636–2645

    PubMed  CAS  Google Scholar 

  • Masui T, Wakefield LM, Lechner JF, La Veck MA, Sporn B, Harris CC (1986) Type-beta transforming growth factor is the primary differentiation-inducing serum factor for normal human bronchial epithelial cells. Proc Natl Acad Sci USA 83: 2438–2442

    Article  PubMed  CAS  Google Scholar 

  • Matrisian LM, Leroy P, Ruhlmann C, Gesnel M-C, Breathnach R (1986) Isolation of the oncogene and epidermal growth factor-induced transin gene: complex control in rat fibroblasts. Mol Cell Biol 6: 1679–1686

    PubMed  CAS  Google Scholar 

  • Moses HL, Leof EB (1986) Transforming growth factor-beta. In: Kahn P, Graf T (eds) Oncogene and Growth Control. Springer, Berlin, Heidelberg, New York, pp. 51–57

    Chapter  Google Scholar 

  • Moses HL, Branum EB, Proper JA, Robinson RA (1981) Transforming growth factor production by chemically transformed cells. Cancer Res 41: 2842–2848

    PubMed  CAS  Google Scholar 

  • Moses HL, Tucker RF, Leof EB, Coffey RJJ, Halper J, Shipley GD (1985) Type-beta transforming growth factor is a growth stimulator and a growth inhibitor. In: Feramisco J, Ozanne B, Stiles C (eds) Growth Factors and Transformation. Cancer Cells, vol 3. Cold Spring Harbor Press, Cold Spring Harbor, pp 65–71

    Google Scholar 

  • Padgett RW, St Johnston RD, Gelbart WM (1987) A transcript from a Drosophila-patterngene predicts a protein homologous to the transforming growth factor-beta family. Nature 325:81–84

    Article  PubMed  CAS  Google Scholar 

  • Postlethwaite AE, Keski-Oja J, Moses HL, Kang AH (1987) Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor-beta. J Exp Med 165: 251–256

    Article  PubMed  CAS  Google Scholar 

  • Raghow R, Postlethwaite AE, Keski-Oja J, Moses HL, Kang H (1987) Transforming growth factor-beta increases steady-state levels of type-I procollagen and fibronectin mRNA posttranscriptionally in cultured human dermal fibroblasts. J Clin Invest 79:1285–1288

    Article  PubMed  CAS  Google Scholar 

  • Roberts AB, Anzano MA, Lamb LC, Smith JM, Sporn MB (1981) New class of transforming growth factors potentiated by epidermal growth factor: isolation from non-neoplastic tissue. Proc Natl Acad Sci USA 78: 5339–5343

    Article  PubMed  CAS  Google Scholar 

  • Roberts AB, Frolik CA, Anzano MA, Sporn MB (1983) Transforming growth factors from neoplastic and non-neoplastic tissues. Fed Proc 42: 2621–2626

    PubMed  CAS  Google Scholar 

  • Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl H, Fauci AS (1986) Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivoand stimulation of collagen formation in vitro. Proc Natl Acad Sci USA 83: 4167–4171

    Article  PubMed  CAS  Google Scholar 

  • Shipley GD, Pittelkow MR, Wille JJJ, Scott RE, Moses L (1986) Reversible inhibition of normal human prokeratinocyte proliferation by type-beta transforming growth factor-growth inhibitor in serum-free medium. Cancer Res 46: 2068–2071

    PubMed  CAS  Google Scholar 

  • Sporn MB, Todaro GJ (1980) Autocrine secretion and malignant transformation of cells. N Engl JMed 303:878–880

    Article  CAS  Google Scholar 

  • Takehara K, LeRoy EC, Grotendorst GR (1987) TGF-beta inhibition of endothelial cell proliferation: alteration of EGF binding and EGF-induced growth-regulatory (competence) gene expression. Cell 49: 415–422

    Article  PubMed  CAS  Google Scholar 

  • Todaro GJ, Fryling C, DeLarco JE (1980) Transforming growth factors produced by certain human tumor cells: Polypeptides that interact with epidermal growth factor receptors. Proc Natl Acad Sci USA 77: 5258–5262

    Article  PubMed  CAS  Google Scholar 

  • Tucker RF, Branum EL, Shipley GD, Ryan RJ, Moses HL (1984a) Specific binding to cultured cells of 125I-labeled transforming growth factor type-beta from human platelets. Proc Natl Acad Sci USA 81: 6757–6761

    Article  PubMed  CAS  Google Scholar 

  • Tucker RF, Shipley GD, Moses HL, Holley RW (1984b) Growth inhibitor from BSC-1 cells closely related to the platelet type-beta transforming growth factor. Science 226: 705–707

    Article  PubMed  CAS  Google Scholar 

  • Twardzik DR, Ranchalis JE, Todaro GJ (1982) Mouse embryonic transforming growth factors related to those isolated from tumor cells. Cancer Res 42: 590–593

    PubMed  CAS  Google Scholar 

  • Wrann M, Bodmer S, de Martin R, Siepl C, Hofer-Warbinek R, Frei K, Hofer E, Fontana A (1987) T cell suppressor factor from human glioblastoma cells is a 12.5-kd protein closely related to transforming growth factor-beta. EMBO J 6: 1633–1636

    PubMed  CAS  Google Scholar 

  • Ying S-Y, Becker A, Ling N, Ueno N, Guillemin R (1986) Inhibin and beta-type transforming growth factor (TGF-beta) have opposite modulating effects on the follicle-stimulating hormone (FSH)-induced aromatase activity of cultured rat granulosa cells. Biochem Biophys Res Commun 136:969–975

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    H. L. Moses, R. M. Lyons, N. J. Sipes, C. C. Bascom & R. J. Coffey Jr.

  2. Department of Virology, University of Helsinki, Helsinki, Finland

    J. Keski-Oja

Authors
  1. H. L. Moses
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  2. J. Keski-Oja
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  3. R. M. Lyons
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  4. N. J. Sipes
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  5. C. C. Bascom
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  6. R. J. Coffey Jr.
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Editors and Affiliations

  1. Department of Pharmacology, Chemotherapy and Toxicology, University of Milan School of Medicine, Via Vanvitelli, 32, 20129, Milan, Italy

    Eugenio E. MÜller , Daniela Cocchi  & Vittorio Locatelli ,  & 

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© 1989 Springer-Verlag Berlin Heidelberg

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Moses, H.L., Keski-Oja, J., Lyons, R.M., Sipes, N.J., Bascom, C.C., Coffey, R.J. (1989). Biological effects of transforming growth factors. In: MÜller, E.E., Cocchi, D., Locatelli, V. (eds) Advances in Growth Hormone and Growth Factor Research. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-11054-6_13

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  • DOI: https://doi.org/10.1007/978-3-662-11054-6_13

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-11056-0

  • Online ISBN: 978-3-662-11054-6

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