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Signal Transduction As a Therapeutic Target

  • Chapter
Attempts to Understand Metastasis Formation III

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 213/3))

Abstract

Cancer therapy is entering a critical period. Conventional approaches for cancer treatment, such as chemotherapy, radiotherapy, or surgery, have obtained results only in lymphoproliferative neoplasms and in a small percentage of solid tumors. The cause of this limited success can be ascribed to several factors, including the poor penetration of drug into tumor masses, biological heterogeneity of cancer cells in primary neoplasms and secondary foci, development of drug resistance, and the ability of malignant cells to invade and metastasize early in the tumorigenic process, often long before the primary tumor is detectable.

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References

  • Akinaga S, Gomik K et al (1991) Antitumor activity of UCN-01, a selective inhibitor of protein kinase C in murine and human tumor models. Cancer Res 51: 4888–4892

    PubMed  CAS  Google Scholar 

  • Akiyama T, Ishida J et al (1987) Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 262: 5592–5595

    PubMed  CAS  Google Scholar 

  • Alberts AW, Chen J et al (1980) Mevinolin: a highly potent competitive inhibitor of hydroxy-methylglutaryl-coenzyme A reductase and a cholesterol lowering agent. Proc Natl Acad Sci USA 77: 3957–3961

    Article  PubMed  CAS  Google Scholar 

  • Albino AP, Schwartz GK et al (1995) Possible roles of bFGF and PKC in the evolution of metastases in malignant melanoma and gastric adenocarcinoma. Bull Inst Pasteur 92: 276–284

    Google Scholar 

  • Andreeson R (1988) Ether lipids in the therapy of cancer. Prog Biochem Pharmacol 22: 118–131

    Google Scholar 

  • Arteaga CL, Johnson MD et al (1991) Elevated content of the tyrosine kinase substrates phospholipase C-y1 in primary human breast carcinomas. Proc Natl Acad Sci USA 88: 10435–10439

    Article  PubMed  CAS  Google Scholar 

  • Bailar JC, Smith E (1986) Progress against cancer? New Engl J Med 314: 1226–1232

    Article  PubMed  Google Scholar 

  • Barbacid M (1987) Ras genes. Annu Rev Biochem 56: 779–827

    Article  PubMed  CAS  Google Scholar 

  • Bargmann CI, Hung MC et al (1986) The neu oncogene encodes an epidermal growth factor-related protein. Nature 319: 226–230

    Article  PubMed  CAS  Google Scholar 

  • Berdel WE (1991) Membrane-interactive lipids as experimental anticancer drugs. Br J Cancer 64: 208–211

    Article  PubMed  CAS  Google Scholar 

  • Berggren M, Gallegos A et al (1993) Inhibition of the signalling enzyme phosphatidylinositol-3-kinase by antitumor ether lipid analogues. Cancer Res 53: 4297–4302

    PubMed  CAS  Google Scholar 

  • Bishop JM (1991) Molecular themes in oncogenesis. Cell 64: 235–248

    Article  PubMed  CAS  Google Scholar 

  • Bos JL (1990) Ras gene mutations and human cancer. Elsevier, Amsterdam

    Google Scholar 

  • Bottaro DP, Rubin JS et al (1991) Identification of the hepatocyte growth factor receptor as the c-met protooncogene product. Science 152: 802–804

    Article  Google Scholar 

  • Boyle WJ, Smeal T et al (1991) Activation of protein kinase C decreases phosphorylation of c-jun at sites that negatively regulate its DNA-binding activity. Cell 64: 573–584

    Article  PubMed  CAS  Google Scholar 

  • Buchdunger E, Trinks U et al (1994) 4,5-Dianilinophtalimide: a protein-tyrosine kinases inhibitor with selectivity for the epidermal growth factor receptor signal transduction pathway and potent in vivo antitumor activity. Proc Natl Acad Sci USA 91: 2334–2338

    Article  PubMed  CAS  Google Scholar 

  • Cantley LC, Auger KR et al (1991) Oncogenes and signal transduction. Cell 64: 281–302

    Article  PubMed  CAS  Google Scholar 

  • Chen R, Sarnecki C et al (1992) Nuclear localization and regulation of erk- and rsk-encoded protein kinases. Mol Cell Biol 12: 915–927

    PubMed  CAS  Google Scholar 

  • Clapham DE (1995) Calcium signaling. Cell 80: 259–268

    Article  PubMed  CAS  Google Scholar 

  • Cole KA, Kohn EC (1994) Calcium-mediated signal transduction: biology, biochemistry, and therapy. Cancer Metastasis Rev 13: 33–41

    Article  Google Scholar 

  • Coughlin SR, Escobedo JA et al (1989) Role of phosphatidylinositol kinase in PDGF receptor signal transduction. Science 243: 1191–1194

    Article  PubMed  CAS  Google Scholar 

  • Davis RJ (1993) The mitogen-activated protein kinase signal transduction pathway. J Biol Chem 268: 14553–14556

    PubMed  CAS  Google Scholar 

  • Delli-Bovi P, Curatola AM et al (1987) An oncogene isolated by transfection of Kaposi’s sarcoma DNA encodes a growth factor that is member of the FGF family. Cell 50: 729–737

    Article  PubMed  CAS  Google Scholar 

  • Deuel TF (1987) Polypeptide growth factors: roles in normal and abnormal cell growth. Annu Rev Cell Biol 3: 443–492

    Article  PubMed  CAS  Google Scholar 

  • Dougall WC, Qian X et al (1994) The neu-oncogene. 9: 2109–2123

    CAS  Google Scholar 

  • Downward J, Yarden Y et al (1984) Close similarity of epidermal growth factor receptor and v-erbB oncogene protein sequences. Nature 307: 521–527

    Article  PubMed  CAS  Google Scholar 

  • Fearon EN, Vogelstein BA (1990) Genetic model for colorectal tumorgenesis. Cell 53: 759–767

    Article  Google Scholar 

  • Felder CC, Ma AL et al (1991) The antiproliferative and antimetastatic compound L651582 inhibits muscarinic acetylcholine receptor-stimulated calcium influx and arachidonic acid release. J Pharmacol Exp Ther 257: 967–971

    PubMed  CAS  Google Scholar 

  • Felder CC, Poulter MO et al (1992) Muscarinic receptor-operated calcium influx in transfected fibroblast cells is independent of inositol phosphates and release of intracellular Ca2+. Proc Natl Acad Sci USA 89: 509–513

    Article  PubMed  CAS  Google Scholar 

  • Felder CC, MacArthur L et al (1993) Tumor-suppressor function of muscarinic acetylcholine receptors is associated with activation of receptor-operated calcium influx. Proc Natl Acad Sci USA 90(5): 1706–1710

    Article  PubMed  CAS  Google Scholar 

  • Felder CC, Singer-Lahat D et al (1994) Voltage-independent calcium channels. Regulation by receptors and intracellular calcium stores. Biochem Pharmacol 48(11): 1997–2004

    Article  PubMed  CAS  Google Scholar 

  • Fidler IJ, Hart IR, (1982) Biologic diversity in metastatic neoplasms - origins and implications. Science 217: 998–1001

    Article  PubMed  CAS  Google Scholar 

  • Fry MJ (1994) Structure, regulation and function of phosphoinositide 3-kinases. Biochim Biopys Acta 1226: 237–268

    CAS  Google Scholar 

  • Furcht L (1986) Critical factors controlling angiogenesis: cell products, cell matrix, and growth factor. Lab Invest 5: 505–509

    Google Scholar 

  • Furuya Y, Lundmo P et al (1994) The role of calcium, pH, and cell proliferation in the programmed (apoptotic) death of androgen-independent prostatic cancer cells induced by thapsigargin. Cancer Res 54: 6167–6175

    PubMed  CAS  Google Scholar 

  • Galkina SI, Sud’lna GF et al (1992) Cell-cell contacts alter intracellular pH. Exp Cell Res 200: 211–214

    Article  PubMed  CAS  Google Scholar 

  • Ganz MB, Pachter JA et al (1990) Multiple receptors coupled to adenylate cyclase regulate Na-H exchange independent of cAMP. J Biol Chem 265: 8989–8992

    PubMed  CAS  Google Scholar 

  • Gazit A, Osherow N et al. (1991) Tyrphostins II: heterocyclic and a-substituted benzylide-nemalono-nitrile tyrphostins as potent inhibitors of EGF receptors and Erb B2/Neu tyrosine kinases. J Med Chem 34: 1897–1907

    Article  Google Scholar 

  • Gibbs JB (1991) Ras C-terminal processing enzymes - new drug targets? Cell 65: 1–4

    Article  PubMed  CAS  Google Scholar 

  • Gibbs JB, Oliff A et al. (1994) Famesyltransferase inhibitors: Ras research yields a potential cancer therapeutic. Cell 77(2): 175–8

    Article  PubMed  CAS  Google Scholar 

  • Goodnight J, Kazanietz MG et al (1992) The cDNA sequence, expression pattern and protein characteristics of mouse protein kinase C-zeta. Gene 122: 305–311

    Article  PubMed  CAS  Google Scholar 

  • Gusovsky F, Lueders JE et al (1993) Muscarinic receptor-mediated tyrosine phosphorylation of phospholipase C-gamma: alternative mechanism for cholinergic receptor-induced phosphoinositide breakdown. J Biol Chem 268: 7768–7772

    PubMed  CAS  Google Scholar 

  • Haag JD, Lindstrom MJ et al (1992) Limonene-induced regression of mammary carcinomas. Cancer Res 52: 4021–4026

    PubMed  CAS  Google Scholar 

  • Hancock JF, Magee Al et al (1989) All ras proteins are polyisoprenylated but only some are palmitoylated. Cell 57: 1167–1177

    Article  PubMed  CAS  Google Scholar 

  • Hennigan RF, Hawker KL et al (1994) Fos-transformation activates genes associated with invasion. Oncogene 9: 3591–3600

    PubMed  CAS  Google Scholar 

  • Hilgard P, Klenner T et al (1993) Alkylphosphocolines: a new class of membrane-active anticancer agents. Cancer Chemother Pharmacol 32: 90–95

    Article  PubMed  CAS  Google Scholar 

  • Holmes K, Chaffins AS et al (1993) Quantitation of human plasma levels of the anticancer agent carboxyamido-triazole by high performance liquid chromatography. J Chrom Biomed Appl 613: 317–325

    Article  CAS  Google Scholar 

  • Irvine RF (1992) Inositol phosphates and Ca++ entry: toward a proliferation or a simplification? Fed Am Soc Exp Biol J 6: 3085–3091

    CAS  Google Scholar 

  • Isakov N, Gopas J et al (1991) Effect of protein kinase C activating tumor promoters on metastases formation by fibrosarcoma cells. Invasion Metastasis 11: 14–24

    PubMed  CAS  Google Scholar 

  • Iyer A, Kmieccik TE et al (1990) Structure, tissue-specific expression, and transforming activity of the mouse met-proto-oncogene. Cell Growth Differ 1: 87–95

    PubMed  CAS  Google Scholar 

  • Kaplan DR, Whitman M et al (1987) Common elements in growth factor stimulation and oncogenic transformation: 85 kD phosphoprotein and phosphatidylinositol kinase activity. Cell 50: 1021–1029

    Article  PubMed  CAS  Google Scholar 

  • Khanavkar B, Ulbrich F et al (1989) Treatment of non-small cell lung cancer with the alkyl-lysophospholipid edelfosine. Contrib Oncol 37: 224

    Google Scholar 

  • Koch CA, Anderson D et al (1991) SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science 252: 668–674

    Article  PubMed  CAS  Google Scholar 

  • Kohl NE, Wilson FR et al (1994) Protein famesyltransferase inhibitors block the growth of rasdependent tumors in nude mice. Proc Natl Acad Sci USA 91: 9141–9145

    Article  PubMed  CAS  Google Scholar 

  • Kohn EC, Liotta LA (1990) L651582, a novel antiproliferative and antimetastasis agent. J Natl Cancer Inst 82: 54–60

    Article  PubMed  CAS  Google Scholar 

  • Kohn EC, Liotta LA (1995) Molecular insights into cancer invasion: strategies for prevention and intervention. Cancer Res 55: 1856–1862

    PubMed  CAS  Google Scholar 

  • Kohn EC, Sandeen MA et al (1992) In vivo efficacy of a novel inhibitor of selected signal transduction pathways including calcium, arachidonate, and inositol phosphates. Cancer Res 52: 3208–3212

    PubMed  CAS  Google Scholar 

  • Kohn EC, Felder CC et al (1994a) Structure-function analysis of signal and growth inhibition by carboxyamido-triazole, CAI. Cancer Res 54: 935–942

    PubMed  CAS  Google Scholar 

  • Kohn EC, Jacobs W et al (1994b) Calcium influx modulates expression of matrix metalloproteinases-2 (72-kDa type IV collagenase, gelatinase A). J Biol Chem 269: 21505–21511

    PubMed  CAS  Google Scholar 

  • Kohn EC, Alessandro R et al (1995) Angiogenesis: role of calcium-mediated signal transduction. Proc Natl Acad Sci USA

    Google Scholar 

  • Kohn EC, Reed E et al (1996) Clinical investigation of a cytostatic calcium influx inhibitor in patients with refractory cancers. Cancer Research (in press)

    Google Scholar 

  • Kovalenko M, Gazit A et al (1994) Selective platelet-derived growth factor receptor kinase blockers reverse sis-transformation. Cancer Res 54: 6106–6114

    PubMed  CAS  Google Scholar 

  • Kypta RM, Goldberg Y et al (1990) Association between the PDGF receptor and members of the src family of tyrosine kinases. Cell 62: 481–492

    Article  PubMed  CAS  Google Scholar 

  • Lagarde AE, Pouyssegur JM (1986) The Na+: H+ antiport in cancer. Biochim Biophys Acta 9: 1–14

    CAS  Google Scholar 

  • Leevers SJ, Marshall CJ (1992) MAP kinase regulation - the oncogene connection. Trends Cell Biol 2: 283–285

    Article  PubMed  CAS  Google Scholar 

  • Lehel S, Lasic Z et al (1994) Collagen type IV stimulates an increase in intracellular calcium in pancreatic acinar cells via activation of phospholipase C. Biochem J 299: 603–611

    Google Scholar 

  • Lester BR, McCarthy JB (1992) Tumor cell adhesion to the extracellular matrix and signal transduction mechanisms implicated in tumor cell motility, invasion and metastasis. Cancer Metastasis Rev 11: 31–44

    Article  PubMed  CAS  Google Scholar 

  • Lev SJ, Blechman M et al (1994) Steel factor and c-kit protooncogene: genetic lessons in signal transduction. Crit Rev Oncog 5: 141–168

    PubMed  CAS  Google Scholar 

  • Levitzki A (1994) Signal-transduction therapy. Eur J Biochem 226: 1–13

    Article  PubMed  CAS  Google Scholar 

  • Liotta LA, Steeg PS et al (1991) Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64: 327

    Article  PubMed  CAS  Google Scholar 

  • Macara IG (1989) Oncogenes and signal transduction. Physiol Rev 69: 797–820

    PubMed  CAS  Google Scholar 

  • Margolis B (1992) Protein with SH2 domain: transducers in the tyrosine kinase signalling pathway. Cell Growth Differ 3: 73–80

    PubMed  CAS  Google Scholar 

  • Markovits J, Linassier C et al (1989) Inhibitory effects of the tyrosine kinase inhibitor genistein on mammalian DNA topoisomerase II. Cancer Res 49: 5111–5117

    PubMed  CAS  Google Scholar 

  • Matrisian L (1992) The matrix-degrading metalloproteinases. Bioessay 14: 455–462

    Article  CAS  Google Scholar 

  • Matter WF, Brown RF et al (1992) The inhibition o1 phosphatidylinositol 3-kinase by quercetin and analogs. Biochem Biophy Res Commun 186: 624–631

    Article  CAS  Google Scholar 

  • Mazzanti M, DeFelice LJ et al (1990) Ion channels in the nuclear envelope. Nature 343: 764–767

    Article  PubMed  CAS  Google Scholar 

  • McCormick F (1993) How receptors turn Ras on. Nature 363: 15–16

    Article  PubMed  CAS  Google Scholar 

  • Millon R, Nicora F et al (1989) Modulation of human breast cancer cell adhesion by estrogens and antiestrogens. Clin Exp Metastasis 7: 405–415

    Article  PubMed  CAS  Google Scholar 

  • Mischak H, Kolch W et al (1991) Expression of protein kinase C genes in hemepoietic cells is cell-type and B-cell differentiation stage specific. J Immunol 147: 3981–3987

    PubMed  CAS  Google Scholar 

  • Naldini L, Weidner KM et al (1991) Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor. EMBO J 10: 2867–2878

    PubMed  CAS  Google Scholar 

  • Neer EJ (1995) Heterotrimeric G proteins: organizers of transmembrane signals. Cell 80: 249–257

    Article  PubMed  CAS  Google Scholar 

  • Nishizuka Y (1992) Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258: 606–614

    Article  Google Scholar 

  • Nixon JS, Bishop J et al (1992) The design and biological properties of potent and selective inhibitors of protein kinase C. Biochem Soc Trans 20: 419–425

    PubMed  CAS  Google Scholar 

  • Noh D, Lee YH et al (1993) Elevated content of phospholipase C-y1 in colorectal cancer tissues. Cancer 73: 36–41

    Article  Google Scholar 

  • Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194: 23–28

    Article  PubMed  CAS  Google Scholar 

  • O’Brian CA, Housey GM et al (1988) Specific and direct binding of protein kinase C to an immobilized tamoxifen analogue. Cancer Res 48: 3626–3629

    PubMed  Google Scholar 

  • Osherow N, Levitzki A (1994) Epidermal growth factor dependent activation of src family kinases. Eur J Biochem 225: 1047–1053

    Article  Google Scholar 

  • Paterson MC, Dietrich KD et al (1991) Correlation between c-erbB-2 amplification and risk of recurrent disease in node-negative breast cancer. Cancer Res 51: 556–567

    PubMed  CAS  Google Scholar 

  • Peles E, Lamprecht R et al (1992) Regulated coupling of the Neu receptor to phosphatidylinositol 3-kinase and its release by oncogenic activation. J Biol Chem 267: 12266–12274

    PubMed  CAS  Google Scholar 

  • Powis G (1994) Recent advances in the development of anticancer drugs that against signaling pathways. Tumori 80: 69–87

    PubMed  CAS  Google Scholar 

  • Powis G, Bonjouklian R et al (1994) Wortmanin, a potent and selective inhibitor of phosphatidylinositol-3-kinase. Cancer Res 54: 2419–2423

    PubMed  CAS  Google Scholar 

  • Powis G, Seewald MJ et al (1992) Selective inhibition of phosphatidylinositol phospholipase C by citotoxic ether lipid analogues. Cancer Res 52: 2835–2840

    PubMed  CAS  Google Scholar 

  • Randriamampita C, Tsein R (1993) Emptying of intracellular Ca2+ stores releases a novel small messenger that stimulates Ca2+ influx. Nature 364: 809–814

    Article  PubMed  CAS  Google Scholar 

  • Reeve J (1991) Mitogenesis and the search for new targets for anticancer drug design. Tumour Biol 12(1): 1

    Article  PubMed  CAS  Google Scholar 

  • Rilemma JA (1989) Possible roles of phospholipase C in the regulation of cell division in normal and neoplastic cells. Med Hypothesis 29: 1–4

    Article  Google Scholar 

  • Rong S, Segal S et al (1994) Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation. Proc Natl Acad Sci USA 91: 4731–4735

    Article  PubMed  CAS  Google Scholar 

  • Sardet C, Counillo L et al (1990) Growth factors induce phosphorylation of the Na+/H+ antiporter, a glycoprotein of 110 kD. Science 247: 723–726

    Article  PubMed  CAS  Google Scholar 

  • Sato H, Takino T et al (1994) A matrix metalloproteinase expressed on the surface of invasive tumor cells. Nature 370: 61–65

    Article  PubMed  CAS  Google Scholar 

  • Savarese DMF, Russell JT et al (1992) Type IV collagen stimulates an increase in intracellular calcium: potential role in tumor cell motility. J Biol Chem 267: 21928–21935

    PubMed  CAS  Google Scholar 

  • Schafer WR, Rine J (1992) Protein prenylation: genes, enzymes, targets and functions. Annu Rev Genetics 30: 209–237

    Article  Google Scholar 

  • Schallier DK, Brunyneel EA et al (1991) Anti-invasive activity of hexadecylophosphocholine in vitro. Anticancer Res 11:1285–1292

    PubMed  CAS  Google Scholar 

  • Schlessinger J, Ullrich A (1992) Growth factor signaling by receptor tyrosine kinases. Neuron 9: 383–391

    Article  PubMed  CAS  Google Scholar 

  • Schu PV, Takegawa K et al (1993) Phophatidyl-inositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting. Science 260: 88–91

    Article  PubMed  CAS  Google Scholar 

  • Schwartz GK, Jiang J et al (1993) Protein kinase C: a novel target for inhibiting gastric cancer cell invasion. J Natl Cancer Inst 85: 402–407

    Article  PubMed  CAS  Google Scholar 

  • Schwartz GK, Redwood SM et al (1990) Inhibition of invasion of invasive human bladder carcinoma cells by protein kinase C inhibitor staurosporine. J Natl Cancer Inst 82: 1753–1756

    Article  PubMed  CAS  Google Scholar 

  • Sebti SM, Tkalcevic GT et al (1991) Lovostatin, a cholesterol biosynthesis inhibitor, inhibits the growth of human H-ras oncogene transformed cells in nude mice. Cancer Commun 3: 141–146

    PubMed  CAS  Google Scholar 

  • Seewald MJ, Olen RA et al (1990) Inhibition of growth factor-dependent inositol phosphate Ca2+ signaling by antitumor ether lipid analogues. Cancer Res 50: 4458–4463

    PubMed  CAS  Google Scholar 

  • Sherr CJ, Rettenmier CW et al (1985) The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell 41: 665–676

    Article  PubMed  CAS  Google Scholar 

  • Short AD, Bian J et al (1993) Intracellular Ca2+ pool content is linked to control of cell growth. Proc Natl Acad Sci USA 90: 4986–4990 188 R. Alessaridro et al.: Signal Transduction As a Therapeutic Target

    Article  PubMed  CAS  Google Scholar 

  • Simon ML, Strathmann MP et al (1991) Diversity of G proteins in signal transduction. Science 252: 802–808

    Article  PubMed  CAS  Google Scholar 

  • Smith MR, Liu YL et al (1990) Inhibition of serum- and Ras-stimulated DNA synthesis by antibodies to phospholipase C. Science 247: 1074–1077

    Article  PubMed  CAS  Google Scholar 

  • Soriano PC, Montgomery R et al (1991) Targeted disruption of the c-src protoncogene leads to osteoporosis in mice. Cell 64: 693–702

    Article  PubMed  CAS  Google Scholar 

  • Taylor JM, Simpson RV (1992) Inhibition of cancer cell growth by calcium channel antagonists in the athymic mouse. Cancer Res 52(9): 2413–2418

    PubMed  CAS  Google Scholar 

  • Thibault A et al (1995) Lovastatin in phase I and II clinical trials (submitted)

    Google Scholar 

  • Thibault A, Samid D, Tompkins AC, Figg WD, Liang B, Patronas N, Hohl RJ, Cooper MR, Venzon DJ, Reed E, Myers CE (1996) A phase I study of lavastatin, in inhibitor of the mevalonate pathway, in patients with cancer. Clin Cancer Res (in press)

    Google Scholar 

  • Uberall F, Oberhuber H et al (1991) Hexadecylphosphocholine inhibits inositol phosphate formation and protein kinase C activity. Cancer Res 51: 807–812

    PubMed  CAS  Google Scholar 

  • Umezawa H, Imoto M et al (1986) Studies on a new epidermal growth factor-receptor kinase inhibitor, erbstatin, produced by MH435-hF3. J Antibiot (Tokyo) 39: 170–173

    CAS  Google Scholar 

  • Velu TJ, Beguinot L et al (1987) Epidermal-growth-factor-dependent transformation by a human EGF receptor proto-oncogene. Science 238: 1408–1410

    Article  PubMed  CAS  Google Scholar 

  • Waterfield MD, Scrace GT et al (1983) Platelet-derived growth factor is structurally related to the putative transforming protei p28sis of simian sarcoma virus. Nature 304: 35–39

    Article  PubMed  CAS  Google Scholar 

  • Williams NG, Roberts TM (1994) Signal transduction pathways involving the raf proto-oncogene. Cancer Metastasis Rev 13: 105–116

    Article  PubMed  CAS  Google Scholar 

  • Yaish P, Gazit A et al (1988) Blocking of EGF-dependent cell proliferation by EGF receptor kinases inhibitors. Science 242: 933–935

    Article  PubMed  CAS  Google Scholar 

  • Zong CS, Wang L (1994) Modulatory effect of the transmembrane domain of the protein kinase encoded by oncogene ros: biological function and substrate interaction. Proc Natl Acad Sci USA 91: 10982–10986

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Signal Transduction and Prevention Unit, Laboratory of Pathology, National Cancer Institute, MSC1500, 10 Center Drive, 20892-1500, Bethesda, MD, USA

    R. Alessandro, J. Spoonster, R. P. Wersto & E. C. Kohn

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  1. R. Alessandro
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  2. J. Spoonster
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  3. R. P. Wersto
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  4. E. C. Kohn
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Editors and Affiliations

  1. Basel Institute for Immunology, Grenzacherstraße 487, CH-4005, Basel, Switzerland

    Ursula Günthert Ph.D., P.D.

  2. Virchow Klinikum, Chirurgische Abteilung, Robert-Rössle-Klinik, Max-Delbrück-Centrum Berlin, Lindenberger Weg 80, D-13122, Berlin, Germany

    Peter M. Schlag M.D.

  3. Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Straße 10, D-13122, Berlin, Germany

    Walter Birchmeier Ph.D.

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Alessandro, R., Spoonster, J., Wersto, R.P., Kohn, E.C. (1996). Signal Transduction As a Therapeutic Target. In: Günthert, U., Schlag, P.M., Birchmeier, W. (eds) Attempts to Understand Metastasis Formation III. Current Topics in Microbiology and Immunology, vol 213/3. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-80071-9_11

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