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Growth Factors and Receptors

  • Chapter
Oncogenes

Overview

Growth factors and growth factor receptors may be involved in the abnormal growth characteristic of cancer, and both entities are encoded by known proto-oncogenes. Growth factors may act as self-stimulants (autocrine control stimulants of nearby cells(paracrine control), or stimulants of distant tissue (hormonal control). Growth factor receptors often are cell surface molecules that trigger internal cascades of events when stimulated by their particular growth factors. “Second messengers” of several varieties transduce or transmit signals from the cell surface to the nucleus, resulting in gene transcription. The sis oncogene is related to the platelet-derived growth factor (PDGF) and is the only known example of a secreted oncogene product. Other oncogenes are related to growth factor receptors containing a tyrosine protein kinase function: erb B is homologous to the epidermal growth factor (EGF) receptor; erb B-2 (neu) is a related oncogene; the fms gene encodes a product similar to the macrophage colony-stimulating factor-1 receptor; the ros oncogene product shows some homology with the insulin receptor. In these instances the normal cellular genes have been rendered transforming by point mutations and/or deletions. Proepidermal growth factor (a precursor of the epidermal growth factor, EGF) shares similarities with the EGF receptor. In addition, it has sequence homology with the mos-oncogene and with the low density lipoprotein receptor gene. The erb A gene shares sequences with the thyroid hormone receptor, a steroid hormone nuclear receptor. Still other growth factors and their receptors appear to play a role in oncogenesis but are not yet associated with known oncogenes and their products. Such proteins include transforming growth factors α and β and the T cell growth factor interleukin-2.

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Bibliography

Growth Factors

Transmembrane Signaling

erb A

  • Debuire B, Henry C, Benaissa M, et al. Sequencing the erb A gene of avian erythroblastosis virus reveals a new type of oncogene. Science 224:1456, 1984.

    Article  PubMed  CAS  Google Scholar 

  • Graf T, Beug H. Role of the v-erb A and v-erb B oncogenes of avian erythroblastosis virus in erythroid cell transformation. Cell 34:7, 1983.

    Article  PubMed  CAS  Google Scholar 

  • Kahn P, Frykberg L, Brady C, et al. v-erb A cooperates with sarcoma oncogenes in leukemic cell transformation. Cell 45:349, 1986.

    Article  PubMed  CAS  Google Scholar 

  • Riedel H, Dall TJ, Schlessinger J, et al. A chimaeric receptor allows insulin to stimulate tyrosine kinase activity of epidermal growth factor receptor. Nature 324:68, 1986.

    Article  PubMed  CAS  Google Scholar 

  • Weinberger C, Hollenberg SM, Rosenfeld MG, et al. Domain structure of human glucocorticoid receptor and its relationship to the v-erb A oncogene product. Nature 318:670, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Weinberger C, Thompson CC, Ong ES, et al. The c-erb A gene encodes a thyroid hormone receptor. Nature 324:641, 1986.

    Article  PubMed  CAS  Google Scholar 

v-sis/PDGF

  • Bowen-Pope DF, Vogel A, Ross R. Production of platelet-derived growth factor-like molecules and reduced expression of platelet-derived growth factor receptors accompany transformation by a wide spectrum of agents. Proc Natl Acad Sci USA 81:2396, 1984.

    Article  PubMed  CAS  Google Scholar 

  • Chiu I-M, Reddy EP, Givol D, et al. Nucleotide sequence analysis identified the human c-sis proto-oncogene as a structural gene for platelet-derived growth factor. Cell 37:123, 1984.

    Article  PubMed  CAS  Google Scholar 

  • Cochran BH, Reffel AC, Stiles CD. Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cell 33:939, 1983.

    Article  PubMed  CAS  Google Scholar 

  • Dalla-Favera R, Gallo RC, Giallongo A, et al. Chromosomal localization of the human homologue (c-sis) of the simian sarcoma virus one gene. Science 218:686, 1982.

    Article  PubMed  CAS  Google Scholar 

  • Deuel TF, Huang JS, Huang SS, et al. Expression of a platelet-derived growth factor-like protein in simian sarcoma virus transformed cells. Science 221:1348, 1983.

    Article  PubMed  CAS  Google Scholar 

  • Doolittle RF, Hunkapillar MW, Hood LE, et al. Simian sarcoma virus one gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science 221:275, 1983.

    Article  PubMed  CAS  Google Scholar 

  • Groffen J, Heisterkamp N, Stephenson JR, et al. c-sis is translocated from chromosome 22 to chromosome 9 in chronic myelocytic leukemia. J Exp Med 158:9, 1983.

    Article  PubMed  CAS  Google Scholar 

  • Josephs SF, Guo C, Ratner L, et al. Human proto-oncogene nucleotide sequences corresponding to the transforming region of simian sarcoma virus. Science 223:486, 1984.

    Article  Google Scholar 

  • Josephs SF, Ratner L, Clarke MF, et al. Transforming potential of human c-sis nucleotide sequences encoding platelet-derived growth factor. Science 225:636, 1984.

    Article  PubMed  CAS  Google Scholar 

  • Niman HL. Antisera to a synthetic peptide of the sis viral oncogene product recognize human platelet-derived growth factor. Nature 307:180, 1984.

    Article  PubMed  CAS  Google Scholar 

  • Rao CD, Igarashi H, Chiu I-M, et al. Structure and sequence of the human c-sis/platelet-derived growth factor 2 (sis/PDGF-2) transcriptional unit. Proc Natl Acad Sci USA 83:2392, 1986.

    Article  PubMed  CAS  Google Scholar 

  • Robbins KD, Devare SG, Reddy EP, et al. In vivo identification of the transforming gene product of simian sarcoma virus. Science 218:1131, 1982.

    Article  PubMed  CAS  Google Scholar 

  • Swan DC, McBride OW, Robbins KC, et al. Chromosomal mapping of the simian sarcoma virus one gene analogue in human cells. Proc Natl Acad Sci USA 79:4691, 1982.

    Article  PubMed  CAS  Google Scholar 

  • Waterfield MD, Scrace GT, Whittle N, et al. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature 304:35, 1983.

    Article  PubMed  CAS  Google Scholar 

v-erb B/EGF Receptor

  • Brown JP, Twardzik DR, Marquardt H, et al. Vaccinia virus encodes a polypeptide homologous to epidermal growth factor and transforming growth factor. Nature 313:491, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Cohen S, Urisho H, Stoscheck C, et al. A native 170,000 epidermal growth factor receptor-kinase in A431 cell membrane vesicles. J Biol Chem 257:1523, 1982.

    PubMed  CAS  Google Scholar 

  • Cowley G, Smith JA, Gusterson B, et al. The amount of EGF receptor is elevated on squamous cell carcinoma. Cancer Cells 1:5, 1984.

    CAS  Google Scholar 

  • Downward J, Yarden Y, Mayes E, et al. Close similarity of epidermal growth factor receptor and v-erb B oncogene protein sequence. Nature 307:521, 1984.

    Article  PubMed  CAS  Google Scholar 

  • Fung Y-KT, Lewis WG, Crittenden LB, et al. Activation of the cellular oncogene c-erb B by LTR insertion: molecular basis for induction of erythroblastosis by avian leukosis virus. Cell 33:357, 1983.

    Article  PubMed  CAS  Google Scholar 

  • Gilmore T, DeClue JE, Martin GF. Protein phosphorylation at tyrosine is induced by the v-erb B gene product in vivo and in vitro. Cell 40:609, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Hayman M, Beug H. Identification of a form of the avian erythroblastosis virus erb B gene product at the cell surface. Nature 309:460, 1984.

    Article  PubMed  CAS  Google Scholar 

  • Liberman TA, Nusbaum HR, Razos N, et al. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumors of glial origin. Nature 313:144, 1985.

    Article  Google Scholar 

  • Lin CR, Chen WS, Kruijer W, et al. Expression cloning of human EGF receptor-complementary DNA: gene amplification and three related messenger RNA production A431 cells. Science 224:843, 1984.

    Article  PubMed  CAS  Google Scholar 

  • Meyers MB, Merluzzi VJ, Spengler BA, et al. Epidermal growth factor receptor is increased in multidrug-resistant Chinese hamster and mouse tumor cells. Proc Natl Acad Sci USA 83:5521, 1986.

    Article  PubMed  CAS  Google Scholar 

  • Shimizu N, Kondo I, Gamou S, et al. Genetic analysis of hyperproduction of epidermal growth factor receptors in human epidermoid carcinoma A431 cells. Somatic Cell Mol Genet 10:45, 1984.

    Article  CAS  Google Scholar 

  • Spurr NK, Solomon E, Jansson M, et al. Chromosomal localization of the human homologue to the oncogenes erb A and B. EMBO J 3:159, 1984.

    PubMed  CAS  Google Scholar 

  • Ullrich A, Coussens L, Hayflick JS, et al. Human epidermal growth factor receptor cDNA sequence and aberrant expression in A431 epidermoid carcinoma cells. Nature 309:418, 1984.

    Article  PubMed  CAS  Google Scholar 

  • Ushiro H, Cohen SJ. Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A431 cell membranes. J Biol Chem 255:8363, 1980.

    PubMed  CAS  Google Scholar 

  • Yamamoto T, Ikawa S, Akiyama T, et al. Similarity of protein encoded by human c-erb B-2 gene to epidermal growth factor receptor. Nature 319:230, 1986.

    Article  PubMed  CAS  Google Scholar 

  • Yokota J, Yamamoto T, Toyoshima K, et al. Amplification of c-erb B-2 oncogene in human adenocarcinomas in vivo. Lancet 1:765, 1986.

    Article  PubMed  CAS  Google Scholar 

FGF

  • Bohlen P, Baird A, Esch F, et al. Isolation and partial molecular characterization of pituitary fibroblast growth factor. Proc Natl Acad Sci USA 81:5364, 1984.

    Article  PubMed  CAS  Google Scholar 

  • Gospodarowicz D, Massoglia S, Chen J, et al. Isolation and pituitary fibroblast growth factor by fast protein liquid chromatography (FPLC); partial chemical and biological characterization. J Cell Physiol 122:323, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Thomas KA, Rios-Candelore M, Fitzpatrick S. Purification and characterization of acidic fibroblast growth factor from bovine brain. Proc Natl Acad Sci USA 81:357, 1984.

    Article  PubMed  CAS  Google Scholar 

neu

  • Akiyama T, Sudo C, Ogawara H, et al. The product of the human c-erb B-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science 232:1644, 1986.

    Article  PubMed  CAS  Google Scholar 

  • Bargmann C, Hung M-C, Weinberg R. The neu oncogene encodes an epidermal growth factor-related protein. Nature 319:226, 1986.

    Article  PubMed  CAS  Google Scholar 

  • Bargmann CI, Hung M-C, Weinberg RA. Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of pi85. Cell 45:649, 1986.

    Article  PubMed  CAS  Google Scholar 

  • Schecter AL, Stern DF, Vaidayanathan L, et al. The neu oncogene: an erb-B-related gene coding a 185,000-Mr tumor antigen. Nature 312:513, 1984.

    Article  Google Scholar 

v-fms/CSF-1 Receptor

  • Anderson SJ, Gonda MA, Rettenbeier CW, et al. Subcellular localization of glycoproteins encoded by the viral oncogene v-fms. J Virol 51:730, 1984.

    PubMed  CAS  Google Scholar 

  • Coussens L, Van Beveren C, Smith D, et al. Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. Nature 320:222, 1986.

    Article  Google Scholar 

  • Kawasaki ES, Ladner MB, Wang AM, et al. Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science 230:291, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Manger R, Najita L, Nichols EJ, et al. Cell surface expression of the McDonough strain of feline sarcoma virus (fms) gene product (gpl40fms). Cell 39:327, 1984.

    Article  PubMed  CAS  Google Scholar 

  • Nienhuis AW, Bunn HF, Turner PH, et al. Expression of the human c-fms proto-oncogene in hematopoietic cells and its deletion in the 5q-syndrome. Cell 42:421, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Rettenmier CW, Chen JH, Roussel MF, et al. The product of the c-fms proto-oncogene: a glycoprotein with associated tyrosine kinase activity. Science 228:320, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Roussel MF, Dull TJ, Rettenmeier CW, et al. Transforming potential of the c-fms protooncogene (CSF-1 receptor). Nature 325:549, 1987.

    Article  PubMed  CAS  Google Scholar 

  • Sherr CJ, Rettenmier CW, Sacca R, et al. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell 41:665, 1985.

    Article  PubMed  CAS  Google Scholar 

GM-CSF

  • Cantrell MW, Anderson D, Cerretti DP, et al. Cloning, sequence, and expression of a human granulocyte/macrophage colony-stimulating factor. Proc Natl Acad Sci USA 82:6250, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Metcalf D. The granulocyte-macrophage colony-stimulating factors. Science 229:16, 1985.

    Article  PubMed  CAS  Google Scholar 

v-ros/Insulin Receptor

  • Kasuga M, Van Obberghen E, Nissley SP, et al. Demonstration of two subtypes of insulin-like growth factor receptors by affinity cross-linking. J Biol Chem 257:53, 1981.

    Google Scholar 

  • Massague J, Czech MP. The subunit structures of two distinct receptors for insulin-like growth factors I and II and their relationship to the insulin receptor. J Biol Chem 257:5028, 1982.

    Google Scholar 

  • Petruzzelli L, Herrera R, Rosen OM. Insulin receptor is an insulin-dependent tyrosine protein kinase: copurification of insulin-binding activity and protein kinase activity to homogeneity from human placenta. Proc Natl Acad Sci USA 81:3327, 1984.

    Article  PubMed  CAS  Google Scholar 

  • Ullrich A, Bell JR, Chen EY, et al. Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature 313:756, 1985.

    Article  PubMed  CAS  Google Scholar 

  • White MF, Maron R, Kahn CR. Insulin rapidly stimulates tyrosine phosphorylation of an Mr-185,000 protein in intact cells. Nature 318:183, 1985.

    Article  PubMed  CAS  Google Scholar 

mos

  • Baldwin GS. Epidermal growth factor precursor is related to the translation product of the Moloney sarcoma virus oncogene mos. Proc Natl Acad Sci USA 82:1921, 1985.

    Article  PubMed  CAS  Google Scholar 

TGF-α/β

  • Anzano MA, Roberts AB, Smith JM, et al. 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 USA 80:6264, 1983.

    Article  PubMed  CAS  Google Scholar 

  • Assoian RK, Komoriya A, Meyers CA, et al. Transforming growth factor-p in human platelets: identification of a major storage site, purification and characterization. J Biol Chem 258:7155, 1983.

    PubMed  CAS  Google Scholar 

  • Bringman T, Lindguist PB, Derynck R. Different transforming growth factor-α species are derived from a glycosylated and palmitoylated transmembrane precursor. Cell 48:429, 1987.

    Article  PubMed  CAS  Google Scholar 

  • Cheifetz S, Weatherbee J, Tsang ML-S, et al. The transforming growth factor β system; a complex pattern of cross reactive ligands and receptors. Cell 48:409, 1987.

    Article  PubMed  CAS  Google Scholar 

  • Derynck R, Jarrett JA, Chen EY, et al. Human transforming growth factor-β cDNA sequence and expression in tumor cell lines. Nature 316:701, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Derynck R, Roberts AB, Winkler ME, et al. Human transforming growth factor-α: precursor structure and expression in E. coli. Cell 38:287, 1984.

    CAS  Google Scholar 

  • Roberts AB, Anzano MA, Wakefield LM, et al. Type β-transforming growth factor: a bifunctional regulator of cellular growth. Proc Natl Acad Sci USA 82:119, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Shipley GD, Tucker RF, Moses HL. Type β-transforming growth factor/growth inhibitor stimulates entry of monolayer cultures of AKR-2B cells into S phase after a prolonged prereplicative interval. Proc Natl Acad Sci USA 82:4147, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Sporn MB, Roberts AB, Wakefield LM, et al. Transforming growth factor-β: biological function and chemical structure. Science 233:532, 1986.

    Article  PubMed  CAS  Google Scholar 

  • Schreiber AB, Winkler ME, Derynck R. Transforming growth factor-α: a more potent angiogenic mediator than epidermal growth factor. Science 232:1250, 1986.

    Article  PubMed  CAS  Google Scholar 

IL-2

  • Knabbe C, Lippman ME, Wakefield LM. Evidence that transforming growth factor-β is a hormonally regulated negative growth factor in human breast cancer cells. Cell 48:417, 1987.

    Article  PubMed  CAS  Google Scholar 

  • Leonard WJ, Depper JM, Crabtree GR, et al. Molecular cloning and expression of cDNAs for the human interleukin-2 receptor. Nature 311:636, 1985.

    Google Scholar 

  • Leonard WJ, Depper JM, Kanehisa M, et al. Structure of the human interleukin-2 receptor gene. Science 230:633, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Morgan DA, Ruscetti FW, Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science 193:1007, 1976.

    Article  PubMed  CAS  Google Scholar 

  • Nikaido T, Shimizu A, Ishida N, et al. Molecular cloning of cDNA encoding human interleukin-2 receptor. Nature 311:631, 1984.

    Article  PubMed  CAS  Google Scholar 

  • Smith KA. Interleukin 2. Annu Rev Immunol 2:319, 1984.

    Article  PubMed  CAS  Google Scholar 

  • Smith KA, Cantrell DA. Interleukin-2 regulates its own receptors. Proc Natl Acad Sci USA 82:864, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Taniguchi T, Matsui H, Takashi F, et al. Structure and expression of a cloned cDNA for human interleukin-2. Nature 302:305, 1983.

    Article  PubMed  CAS  Google Scholar 

IL-3

  • Ihle JN, Keller J, Henderson L, et al. Biological properties of homogeneous interleukin-3: demonstration of WEH1–3 growth factor activity, mast cell growth factor activity, P-cell stimulating activity, colony stimulating factor activity, and histamine producing cell stimulating factor activity. J Immunol 131:282, 1983.

    PubMed  CAS  Google Scholar 

Other Growth Factors

  • Bauknecht T, Kiechle M, Bauer G, et al. Characterization of growth factors in human ovarian carcinomas. Cancer Res 46:2614, 1986.

    PubMed  CAS  Google Scholar 

  • Cuttita F, Carney DN, Mulshine J, et al. Bombesin-like peptides can function as autocrine growth factors in human small cell lung cancer. Nature 316:823, 1985.

    Article  Google Scholar 

  • Huff KK, Kaufmann D, Gabby HH, et al. Secretion of an insulin-like growth factor-I-related protein by human breast cancer cells. Cancer Res 46:4613, 1986.

    PubMed  CAS  Google Scholar 

  • Klagsbrun M, Sasse J, Sullivan R, et al. Human tumor cells synthesize an endothelial cell growth factor that is structurally related to basic fibroblast growth factor. Proc Natl Acad Sci USA 83:2448, 1986.

    Article  PubMed  CAS  Google Scholar 

  • Liotta LA, Mandler R, Murano G, et al. Tumor cell autocrine motility factor. Proc Natl Acad Sci USA 83:3302, 1986.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Kasier Foundation Hospital, 2425 Geary Blvd, 94115, San Francisco, California, USA

    Kathy B. Burck M.D., Ph.D.

  2. Lineberger Cancer Research Center, University of North Carolina at Chapel Hill, 27514, Chapel Hill, North Carolina, USA

    Edison T. Liu M.D. (Assistant Professor of Medicine/Oncology School of Medicine Member)

  3. GENELABS, Inc., 505 Penobscott, 94063, Redwood City, California, USA

    James W. Larrick M.D., Ph.D. (Director of Exploratory Research, Senior Research Scientist)

  4. Psoriasis Research Scientist, Box V, 94305, Stanford, California, USA

    James W. Larrick M.D., Ph.D. (Director of Exploratory Research, Senior Research Scientist)

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  1. Kathy B. Burck M.D., Ph.D.
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  2. Edison T. Liu M.D.
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  3. James W. Larrick M.D., Ph.D.
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© 1988 Springer-Verlag New York Inc.

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Burck, K.B., Liu, E.T., Larrick, J.W. (1988). Growth Factors and Receptors. In: Oncogenes. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-3718-1_8

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  • DOI: https://doi.org/10.1007/978-1-4612-3718-1_8

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  • Print ISBN: 978-0-387-96423-2

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