Abstract
An explosive pace of research has developed in the last several years exploring the role of oncogenes and their products (see preceding Chapters, 10–14, this volume). The potential of elucidating the molecular mechanisms operative in neoplastic transformation has generated widespread excitement and research interest within the scientific community, particularly among cancer biologists. A large component of research performed in this area has been directed towards understanding the biochemical and molecular basis of the initiation and promotion of the transformed phenotype of cells that have undergone oncogenic transfection in cell culture (4, 26, 46, 47, 51, 89, 90). A variety of studies have also indicated that oncogenes and their products may also contribute to additional aspects of tumor progression (5, 46, 47, 62, 87). Most recently, a number of research groups have carried out investigations to ascertain whether oncogenes and their encoded gene products contribute to the progressive stages of malignant neoplastic growth resulting in tumor invasion in tumor invasion and metastatic spread (1, 6, 7, 19, 20, 21, 22, 49, 68, 80, 85).
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References
Albino AP, Le Strange R, Oliff AI, Furth ME, Old LJ: (1984). Transforming ras genes from human melanoma: a manifestation or tumour heterogeneity? Nature 308:69–71.
Albini A, Iwamoto Y, Kleinman HK et al: (1987). A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res 47:3239–3245.
Astrin SM, Rothberg PG: (1983). Oncogenes and Cancer. Cancer Investig 1:355–364.
Balmain A: Transforming ras oncogenes and multistage carcinogenesis. (1985). Br J Cancer 51:1–7.
Becker FF: Tumor phenotype and susceptibility to progression as an expression of subpopulations of initiated murine cells. (1985). Cancer Res 45:786–773.
Bernstein SC, Weinberg RA: Expression of the metastatic phenotype in cells transfected with human metastatic tumor DNA. (1985). Proc Natl Acad sci (USA) 82:1726–1730.
Bondy GP, Wilson S, Chambers AF: (1985). Experimental metastatic ability of H-ras-transformed NIH3T3 cells. Cancer Res 45:6005–6009.
Bradley MO, Kraynak AR, Storer RD et al: (1986). Experimental metastasis in nude mice of NIH3T3 cells containing various ras genes. Proc Natl Acad sci (USA) 83:5277–5281.
Brodeur GM, Seeger RC, Schwab M, Varmus HE, Bishop JM: (1984). Amplication of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 224:1121–1124, 1984
Brunson KW, Goldfarb RH: (1988). Immunosuppression by metastatic tumors. In: HE, Kaiser (ed.). Cancer Growth and Progression
Brunson KW, and Nicolson, GL: (1978). Selection and biologic properties of malignant variants of a murine lymphosarcoma. J Natl Cancer Inst 61:1499–1503.
Brunson KW, Nicolson GL: (1980). Experimental brain metastasis. In. L. Weiss, HA, Gilbert, JB, Posner (Eds.). Brain Metastasis. GK, Hall and Co., Boston, pp 50–65.
Chambers AF, Wilson, S: (1985). Cells transformed with a ts viral src mutant are temperature sensitive for in vivo growth. Molec Cell Biol 5: 728–733.
Collard JG, van Beek WP, Janssen JWG, Schijven JF: (1985). Transfection by human oncogenes: Concomitant induction of tumorigenicity and tumor-associated membrane alterations. Int J Cancer 35:207–214.
Collard JG, Schijven JF, Roos E: (1987). Invasive and metastatic potential induced by ras-transfection into mouse BW5147 T-lymphoma cells. Cancer Res 47:754–759.
Cook, JL, Lewis AM: (1984). Differential NK cell and macrophage killing of hamster cells infected with nononcogenic or oncogenic adenovirus. Science 224:612–616.
Dotto GP, Parada LF, Weinberg RA: (1985). Specific growth response of ras-transformed embryo fibroblasts to tumor promoters. Nature 318:472–475.
Duesberg PH: (1985). Activated proto-onc genes: sufficient or necessary for cancer? Science 228:669–667.
Eccles SA, Marshall C, Vousden K, Purvies H: (1985). Enhanced metastatic capacity of mouse mammary carcinoma cells transfected with H-RAS. Brit J Cancer 51:586.
Egan SE, McClarty GA, Wright JA, Greenberg AH: (1986). H-RAS transcriptional activation and metastasis formation. J Cellular Biochem Suppl 10A, 51 (Abstract A134).
Eisenbach L, Feldman M: (1985). Genes and antigens controlling tumor metastases. In. Neth, Gallo, Greaves and Janka, Eds. Haematology and Blood Transfusion, Vol. 29. Modern Trends in Leukemia VI. Springer Verlag Berlin pp 499–507.
Erisman MD, Rothberg PG, Diehl RE, Morse CC, Spandorfer JM, Astrin SM: (1985). Deregulation of c-myc gene expression in human colon carcinoma is not accompanied by amplification or rearrangement of the gene. Molec Cell Biol 5:1969–1976.
Fermisco JR, Clark R, Wong G, Arnheim N, Milley R, McCormick F: (1985). Transient reversion of ras oncogene-induced cell transformation by antibodies specific for amino acid 12 of ras protein. Nature 314:639–642.
Gallick GE, Kurzrock R, Kloetzer WS, Arlinghaus RB, and Gutterman, JU: (1985). Expression of p21 ras in fresh primary and metastatic human colorectal tumors. Proc Natl Acad Sci (U.S.A.) 82: 1795–1799.
Garbisa S, Pozzatti R, Muschel R, Saffiotti U, Ballin M, Goldfarb, RH, Khoury G, Liotta LA: (1987). Secretion of type IV collagenolytic protease and metastatic phenotype: Induction by transfection with c-Ha-ras but not c-Ha-ras plus Ad2-Ela. Cancer Res 47:1523–1528.
Glaichenhaus N, Mougneau E, Connan G, Rassoulzadegan M, Cuzin, F: (1985). Cooperation between multiple oncogenes in rodent embryo fibroblasts: An experimental model of tumor progression? Adv Cancer Res 45:291–305.
Goldfarb RH: (1986a). Proteolytic enzymes in tumor invasion and degradation of host extracellular matrices. In. KV. Honn, WE, Powers, BF Sloane, Eds. Mechanisms of Cancer Metastasis: Potential Therapeutic Implications. Martinus Nijhoff, Boston, pp 341–375.
Goldfarb RH: (1986b). Cell-Mediated Cytotoxic Reactions. Human Pathology 17:138–145
Goldfarb RH, Liotta LA: (1986). Proteolytic enzymes in cancer invasion and metastasis. Seminars in Thrombosis and Hemostasis. 12:294–307
Goldfarb RH, Quigley JP: (1978). Synergistic effect of tumor virus transformation and tumor promoter treatment on the production of plasminogen activator by chick embryo fibroblasts. Cancer Res 38:4601–4609
Goldfarb RH, Quigley JP: (1980). Purification of plasminogen activator from Rous sarcoma virus transformed chick embryo fibroblasts treated with the tumor promoter phorbol 12-myristate-13-acetate. Biochem 19:5463–5471
Goldfarb RH, Brunson KW: (1987). Overview of current understanding of tumor spread. In. HE, Kaiser, Ed. Cancer Growth and Progression, Vol. I, Martinus Nijhoff, Boston, In Press
Green AR, Wyke JA: (1985). Anti-Oncogenes. A subset of regulatory genes involved in carcinogenesis? The Lancet. August 31. 475–477
Greenberg AH, Egan SE, Jaroli, L. et al: (1987). Natural killer cell regulation of implantation and early lung growth of H-ras-transformed 10T1/2 fibroblasts in mice. Cancer Res 47:4801–4805.
Greenhalgh DA, Kinsella AR: (1985). C-Ha-ras not c-Ki-ras activation in three colon tumor cell lines. Carcinogen 6:1533–1535
Greig RG, Koestler TP, Trainer DL, Corwin SP, Miles L, Kline T, Sweet R, Yokoyama S, Poste G: (1985b). Tumorigenic and metastatic properties of “normal” and ras-transfected NIH-3T3 cells. Proc Natl Acad sci (USA) 82:3698–3701
Hand PH, Thor A, Wunderlich D, Muraro R, Caruso A, Schlom J: (1984). Monoclonal antibodies of predefined specificity detect activated ras gene expression in human mammary and colon carcinomas. Pros Natl Acad sci (USA) 81:5227–5231
Hart IR: (1985). Molecular basis of tumor spread. Nature 315:275
Heighway J, Hasleton PS (1986). C-Ki-ras amplification in human lung cancer. Br J Cancer 53:285–287
Heppner GH: (1986). Problems posed for cancer treatment by tumor cell heterogeneity. In. KV Honn, WE Powers, BF Sloane, Eds. Mechanisms of cancer Metastasis. Potential Therapeutic Implications. Martinus Nijhoff. Boston pp. 69–79
Hsiao W.-L. W, Gattoni-Celli S, Weinstein IB: (1984). Oncogene-induced transformation of C3H 10T1/2 cells is enhanced by tumor promotors. Science. 226:552–555
Johnson PW, Baubock C, Roder JC: (1985). Transfection of a rat cell line with the v-Ki-ras oncogene is associated with enhanced susceptibility to natural killer cell lysis. J Exp Med 162:1732–1737
Kasid A, Lippman ME, Papageorge AG, Lowy DR and Gelmann, EP: (1985). Transfection of v-ras H DNA into MCF-7 human breast cancer cells bypasses dependence on estrogen for tumorigenicity. Science 228:725–728
Kerr IB, Lee FD, Quintanilla M, Balmain A: (1985). Immunocytochemical demonstration of p21 ras family oncogene product in normal mucosa and in premalignant and malignant tumors of the colorectum. Br J Cancer 52:695–700
Kerr IB, Spandidos DA, Finlay IG, Lee FD, McArdle CS: (1986). The relation of ras family oncogene expression to conventional staging criteria and to clinical outcome in colorectal carcinoma. Br J Cancer 53:231–235
Klein G, Klein E: (1984). Oncogene activation and tumor progression. Carcinogenesis. 5:429–435
Klein G, Klein E: (1985). Evolution of tumours and the impact of molecular oncology. Nature 315:190–195
Kris RM, Avivi A, Bar-Eli M, Alon Y, Carmi P, Schlessinger J, Raz A: (1985). Expression of KI-RAS oncogene in tumor cell variants exhibiting different metastatic capabilities. Int J Cancer 35:227–230
Kung H-F, Smith MR, Bekesi E, Manne V, Stacey DW: (1986). Reversal of transformed phenotype by monoclonal antibodies against Ha-ras p21 proteins. Exper Cell Res 162:363–371
Kurzrock R, Gallick GE, Gutterman JU: (1986). Differential expression of p21ras gene products among histological subtypes of fresh primary human lung tumors. Cancer Res 46:1530–1534
Land H, Parada LF, Weinberg RA: (1983a). Cellular oncogenes and multistep carcinogenesis. Science 222:771–778
Land H, Parada LF, Weinberg RA: (1983b). Tumorigenic conversion of primary embryo fibroblasts require at least two cooperating oncogenes. Nature 304:596–602
Lanza LA, Wilson DJ, Ikerji B et al: (1987). Human oncogene-transfected tumor cells display differential susceptibility to lysis by LAK and natural killer cells. J Immunol 137:2716–2720.
Liotta LA: (1986a). Tumor invasion and metastasis-role of the extracellular matrix. Rhoads Memorial Award Lecture. Cancer Res 46:1–7
Liotta LA: (1986b). Molecular biology of metastases: A review of recent approaches. Eur J Cancer Clin Oncol 22:345–348
Liotta LA, Goldfarb RH, Brundage R, Siegal GP, Terranova V, Garbisa S: (1981). Effect of plasminogen activator (urokinase), plasmin, and thrombin on glycoprotein and collagenous components of basement membrane. Cancer Res 41:4629–4636
Little CD, Nau MM, Carney DN, Gazdar AF, Minna JD: (1983). Amplification and expression of the c-myc oncogene in human lung cancer cells. Nature 306:194–196
Mareel MM, Van Roy FM: (1986). Are oncogenes involved in invasion and metastasis? Anticancer Res 6:419–436
Masui H, Kawamoto T, Sato JD, Wolf B, Sato G, Mendelsohn J: (1984). Inhibition of human tumor cells in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies. Cancer Res. 44:1002–1007
Muschel RJ, Williams JE, Lowy DR, Liotta LA: (1985). Harvey ras induction of metastatic potential depends upon oncogene activation and the type of recipient cell. Amer J Pathol 121:1–8
Nau MM, Brooks BJ, Battey J, Sausville E, Gazdar AF, Kirsch IR, McBride OW, Bertness V, Hollis GF, Minna JD: (1986). L-myc, a new myc-related gene amplified and expressed human small cell lung cancer Nature 318:69–73
Nicolson GL: (1984). Tumor progression, oncogenes and the evolution of metastatic phenotypic diversity. Clin Expl Metastasis. 2:85–105.
Niman HL, Thompson AMH, Yu A, Markman MK, Willems JJ, Herwig KR, Habib NA, Wood CB, Houghten RA, Lerner RA: (1985). Anti-peptide antibodies detect oncogene-related proteins in urine. Froc Natl Acad sci (U.S.A) 82:7924–7928
Nowell, PC: (1986). Perspectives in Cancer Research: Mechanisms of Tumor Progression. Cancer Res 46:2203–2207
Ohuchi N, Thor A, Page DL, Hand PH, Halter SA, Schlom, J: (1986). Expression of the 21,000 molecular weight ras protein in a spectrum of benign and malignant human mammary tissues. Cancer Res 46:2511–2519
Poste G: (1984). Hype, hope and honesty. Biotechnology. December, 1984:1096
Poste G: (1986). Pathogenesis of metastatic disease: Implications for current therapy and for the development of new therapeutic strategies. Cancer Treat Rep 70:183–199
Pozzatti R, Muschel R, Williams J, Padmanabhan R, Howard B, Liotta L, Khoury G: (1986). Primary rat embryo cells transformed by one or two oncogenes show different metastatic potentials. Science 232:223–227
Rothberg PG, Spandorfer JM, Erisman MD, Staroscik RN, Sears HF, Petersen RO, Astrin SM (1985). Evidence that C-myc expression defines two genetically distinct forms of colorectal adenocarcinoma. Br J Cancer 52:629–632
Rotter V, Wolf D, Blick M, Nicolson GL: (1985). Expression of abl and other oncogenes is independent of metastatic potential in Abelson virus-transformed malignant murine large cell lymphoma. Clin Expl Metastasis 3: 77–86
Sager R: (1985a). Genetic suppression of tumor formation. Adv. Cancer Res 44:43–68
Sager R, Craig RW: (1985b). Anti-oncogenes and the suppression of tumor formation. In: J Feramisco, B Ozanne, C Stiles, Eds Cancer Cells Volume 3. Growth Factors and Transformation. Cold Spring Harbor Laboratory Press, Cold Spring Harbor Laboratory, pp. 95–100
Sager R: (1986). Genetic suppression of tumor formation: A new frontier in cancer research. Cancer Res 46:1573–1580
Samid D, Chang EH, Friedman RM: (1985). Development of transformed phenotype induced by a human ras oncogene is inhibited by interferon. Biochem Biophys Res Comm 126:509–516
Schirrmacher V: (1985). Cancer metastasis: Experimental approaches, theoretical concepts, and impacts for treatment strategies. Adv in Cancer Res 43:1–73
Shimizu, K, Goldfarb M, Suard Y, Perucho, M, Li Y, Kamata T, Feramisco J, Stavenezer E, Fogh J, Wigler MH: (1983). Three human transforming genes are related to the viral ras oncogenes. Proc Natl Acad sci (USA) 80:2113–2116
Sistonen L, Keski-Oja J, Ulmanen I, Holtta E, Wikgren B-J, Alitalo K: (1987). Dose effects of transfected c-Ha-ras val 12 oncogene in transformed cell clones. Exp Cell Res 168(2):518–30
Taya Y, Hosogai K, Hirohashi S, Shimosato Y, Tsuchiya R, Tsuchida N, Fushimi M, Sekiyua T, Nishimura S: (1984). A novel combination of K-ras and myc amplification accompanied by point mutational activation of K-ras in a human lung cancer. EMBO J 3:2943–2946
Thor A, Hand PH, Wunderlich D, Caruso A, Muraro R, Schlom J: (1984). Monoclonal antibodies define different ras gene expression in malignant and benign colonic diseases. Nature 311:562–565.
Thorgeirsson UP, Turpeenniemi-Hujanen T, Williams JE, Westin EH, Heilman CA, Talmadge JE, Liotta LA: (1984). NIH/3T3 cells transfected with human tumor DNA containing activated ras oncogenes express the metastatic phenotype in nude mice. Molec Cell Biol 5:259–262
Thorgeirsson UP, Turpeenniemi-Hujanen T, Liotta LA: (1985). Cancer cells, components of basement membranes, and proteolytic enzymes. Int. Rev Expt Path 27:203–234
Thorgeirsson UP, Turpeenniemi-Hujanen T, Talmadge, JE, Liotta LA: (1986). In. Welch DR, Bhuyan DK, Liotta LA (eds). Cancer Metastasis. Experimental and clinical Strategies. (Prog, in Clin, and Biol. Res., Vol. 212) Alan R, Liss, New York. pp. 77–95
Valenzuela DM, Groffen J: (1986). Four human carcinoma cell lines with novel mutations in position 12 of c-K-ras oncogene. Nucl Acids Res 14:843–852
Viola MV, Fromowitz F, Oravez S, Deb S, Finkel G, Lundy J, Hand P, Thor A, Schlom J: (1986). Expression of ras oncogene p21 in prostate cancer. New Eng J Med 314–133–137
Vousden KH, Marshall CJ: (1984). Three different activated ras genes in mouse tumors; evidence for an oncogene activation during progression of a mouse lymphoma. EMBO J 3:913–917
Wallich R, Bulbuc N, Hammerling GJ, Katzav S, Feldman, M: (1985). Abrogation of metastatic properties of tumor cells by de novo expression of H-2K antigens following H-2 gene transfection. Nature 315:301–305
Welch DR, Tomasovic SP: (1985). Implications of tumor progression on clinical oncology. Clin Expl Metastasis 3:151–188
Yancopoulos GD, Nisen PD, Tesfaye A., Kohl NE, Goldfarb MP, Alt FW: (1985). N-myc can cooperate with ras to transform normal cells in culture. Proc Natl Acad sci (U.S.A.) Proc Natl Acad sci 82:5455–5459
Yoakum GH, Lechner JF, Gabrielson EW, Korba BE, Malan-Shibley L, Willey JC, Valerio MG, Shamsuddin AM, Trump BF, Harris CC: (1985). Transformation of human bronchial epithelial cells transfected by Harvey ras oncogene. Science 221:1174–1179
Yokota J, Tsunetsugu-Yokota Y, Battifora H, Le Fevre C, Cline MJ: (1986). Alterations of myc, myb, and ras Ha protooncogenes in cancers are frequent and show clinical correlation. Science. 231:261–265
Yuhki N, Hamada J, Kuzumakai N, Takeichi N, Kobayashi H: (1986). Metastatic ability and expression of c-fos oncogene in cell clones of a spontaneous rat mammary tumor. Jpn J Cancer Res (Gann) 77:9–12
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Goldfarb, R.H., Brunson, K.W. (1989). Oncogene Products as Potential Therapeutic Targets for Control of Established Metastatic Disease. In: Weisburger, E.K. (eds) Mechanisms of Carcinogenesis. Cancer Growth and Progression, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-2526-7_15
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