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Oncogenes, Tumor Suppressor Genes and Apoptosis-Inducing Genes Utilized in Cancer Gene Therapy

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Gene Therapy for Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Oncogenes, tumor suppressor genes, and apoptosis-inducing genes play critical roles in cell proliferation, differentiation, and death. Their expressions are frequently altered in cancer cells by gene mutation, deletion, rearrangement, inactivation, or overexpression. Some of these alterations are directly related to the development and maintenance of malignant phenotypes; others relate to the response of cancer cells to various anticancer therapies. Both preclinical and clinical studies have indicated that restoring the normal function of these genes may be an effective means of cancer therapy although full realization of any anticancer benefit will depend on effective delivery of these genes to cancer cells.

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References

  1. Knudson AG. Two genetic hits (more or less) to cancer. Nature Reviews Cancer, 2001;1: 157–162.

    Article  PubMed  CAS  Google Scholar 

  2. Yokota J. Tumor progression and metastasis. Carcinogenesis, 2000;21:497–503.

    Article  PubMed  CAS  Google Scholar 

  3. Fearnhead NS, Wilding JL, Bodmer WF. Genetics of colorectal cancer: hereditary aspects and overview of colorectal tumorigenesis. Br Med Bull 2002;64:27–43.

    Article  PubMed  CAS  Google Scholar 

  4. Parker JE, Mufti GJ. The Myelodysplastic syndromes: A matter of life or death. Acta Haematol 2003;111:78–99.

    Article  Google Scholar 

  5. Urbain JL. Oncogenes, cancer and imaging. J Nucl Med 1999;40:498–504.

    PubMed  CAS  Google Scholar 

  6. Macleod K. Tumor suppressor genes. Curr Opin Genet Dev 2000; 10:81–93.

    Article  PubMed  CAS  Google Scholar 

  7. Daniel PT, Wieder T, Sturm I, Schulze-Osthoff K. The kiss of death: promises and failures of death receptors and ligands in cancer therapy. Leukemia 2001;15:1022–1032.

    Article  PubMed  CAS  Google Scholar 

  8. Adams JM, Cory S. The Bcl-2 protein family: Arbiters of cell survival. Science 1998;281:1322–1326.

    Article  PubMed  CAS  Google Scholar 

  9. Colledge WH, Richardson WD, Edge MD, Smith AE. Extensive Mutagenesis of the Nuclear Location Signal of Simian Virus-40 Large-T Antigen. Mol Cell Biol 1986;6:4136–4139.

    PubMed  CAS  Google Scholar 

  10. Varmus HE. Form and Function of Retroviral Proviruses. Science 1982;216:812–820.

    Article  PubMed  CAS  Google Scholar 

  11. Stehelin D, Varmus HE, Bishop JM, Vogt PK. Dna Related to Transforming Gene(S) of AvianSarcoma Viruses Is Present in Normal Avian Dna. Nature 1976;260:170–173.

    Article  PubMed  CAS  Google Scholar 

  12. Rhim JS. Viruses, Oncogenes, and Cancer. Cencer Detect Prev 1988;11:139–149.

    CAS  Google Scholar 

  13. Perucho M, Goldfarb M, Shimizu K, Lama C, Fogh J, Wigler M. Human-Tumor-Derived Cell-Lines Contain Common and Different Transforming Genes. Cell 1981;27:467–476.

    Article  PubMed  CAS  Google Scholar 

  14. Bell JC. Oncogenes. Cancer Lett 1988;40:1–5.

    Article  PubMed  CAS  Google Scholar 

  15. Pietras K, Sjoblom T, Rubin K, Heldin CH, Ostman A. PDGF receptors as cancer drug targets. Cancer Cell 2003;3:439–443.

    Article  PubMed  CAS  Google Scholar 

  16. Mechtersheimer G, Egerer G, Hensel M, et al. Gastrointestinal stromal tumours and their response to treatment with the tyrosine kinase inhibitor imatinib. Virchows Archiv 2004;444:108–118.

    Article  PubMed  CAS  Google Scholar 

  17. Shimizu A, O’Brien KP, Sjoblom T, et al. The dermatofibrosarcoma protuberans-associated collagen type I alpha 1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB. Cancer Res 1999;59:3719–3723.

    PubMed  CAS  Google Scholar 

  18. Fleming TP, Saxena A, Clark WC, et al. Amplification and Or Overexpression of Platelet-Derived Growth-Factor Receptors and Epidermal Growth-Factor Receptor in Human Glial Tumors. Cancer Res 1992;52:4550–4553.

    PubMed  CAS  Google Scholar 

  19. Heinrich MC, Corless CL, Duensing A, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science 2003;299:708–710.

    Article  PubMed  CAS  Google Scholar 

  20. Golub TR, Barker GF, Lovett M, Gilliland DG. Fusion of Pdgf Receptor-Beta to A Novel Ets-Like Gene, Tel, in Chronic Myelomonocytic Leukemia with T(512) Chromosomal Translocation. Cell 1994;77:307–316.

    Article  PubMed  CAS  Google Scholar 

  21. Ciardiello F, De Vita F, Orditura M, Tortora G. The role of EGFR inhibitors in nonsmall cell lung cancer. Curr Opin Oncol, 2004;16:130–135.

    Article  PubMed  CAS  Google Scholar 

  22. Yano S, Kondo K, Yamaguchi M, et al. Distribution and function of EGFR in human tissue and the effect of EGFR tyrosine kinase inhibition. Anticancer Res 2003;23:3639–3650.

    PubMed  CAS  Google Scholar 

  23. Hirsch FR, Varella-Garcia M, Bunn PA, et al. Epidermal growth factor receptor in non-small-cell lung carcinomas: Correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol 2003;21:3798–3807.

    Article  PubMed  CAS  Google Scholar 

  24. Vlahovic G, Crawford J. Activation of tyrosine kinases in cancer. Oncologist 2003;8:531–538.

    Article  PubMed  CAS  Google Scholar 

  25. Bos JL. Genetic Mechanisms in Tumor Initiation and Progression.10. the Ras Gene Family and Human Carcinogenesis. Mutation Res 1988; 195:255–271.

    PubMed  CAS  Google Scholar 

  26. Campbell PM, Der CJ. Oncogenic Ras and its role in tumor cell invasion and metastasis. Sem Cancer Biol 2004; 14:105–114.

    Article  CAS  Google Scholar 

  27. Osada H, Takahashi T. Genetic alterations of multiple tumor suppressors and oncogenes in the carcinogenesis and progression of lung cancer. Oncogene 2002;21:7421–7434.

    Article  PubMed  CAS  Google Scholar 

  28. Sandberg AA. Chromosomes and Causation of Human Cancer and Leukemia — 40 the Ph1 and Other Translocations in Cml. Cancer 1980;46:2221–2226.

    Article  PubMed  CAS  Google Scholar 

  29. Deklein A, Vankessel AG, Grosveld G, et al. A Cellular Oncogene Is Translocated to the Philadelphia-Chromosome in Chronic Myelocytic-Leukemia. Nature 1982;300:764–767.

    Google Scholar 

  30. Apperley JF, Gardembas M, Melo JV, et al. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. New Engl J Med 2002;347:481–487.

    Article  PubMed  CAS  Google Scholar 

  31. Munger K. Disruption of oncogene/tumor suppressor networks during human carcinogenesis. Cancer Invest 2002;20:71–81.

    Article  PubMed  CAS  Google Scholar 

  32. Stanbridge EJ. Genetic-Analysis of Human Malignancy Using Somatic-Cell Hybrids and Monochromosome Transfer. Cancer Surv 1988;7:317–324.

    PubMed  CAS  Google Scholar 

  33. Misra BC, Srivatsan ES. Localization of Hela-Cell Tumor-Suppressor Gene to the Long Arm of Chromosome-Ii. Am J Hum Genet 1989;45:565–577.

    PubMed  CAS  Google Scholar 

  34. Goodrich DW, Lee WH. The Molecular-Genetics of Retinoblastoma. Cancer Surv 1990;9:529–554.

    PubMed  CAS  Google Scholar 

  35. Lee WH, Bookstein R, Hong F, et al. Human Retinoblastoma Susceptibility Gene — Cloning, Identification, and Sequence. Science 1987;235:1394–1399.

    Article  PubMed  CAS  Google Scholar 

  36. Bookstein R, Lee EYHP, To H, et al. Human Retinoblastoma Susceptibility Gene — Genomic Organization and Analysis of Heterozygous Intragenic Deletion Mutants. Proc Natl Acad Sci USA 1988;85:2210–2214.

    Article  PubMed  CAS  Google Scholar 

  37. Fang B, Roth JA. Tumor-suppressing gene therapy. Cancer Biol Ther 2003;2:S115–S121.

    PubMed  CAS  Google Scholar 

  38. Bringold F, Serrano M. Tumor suppressors and oncogenes in cellular senescence. Exper Gerontol 2000;35:317–329.

    Article  CAS  Google Scholar 

  39. Lowe SW. Activation of p53 by oncogenes. Endocrine-Related Cancer 1999;6:45–48.

    Article  PubMed  CAS  Google Scholar 

  40. Bhojani MS, Rossu BD, Rehemtulla A. TRAIL and anti-tumor responses. Cancer Biol Ther 2003;2:S71–S78.

    PubMed  CAS  Google Scholar 

  41. Green DR, Reed JC. Mitochondria and apoptosis. Science 1998;281:1309–1312.

    Article  PubMed  CAS  Google Scholar 

  42. Verhagen AM, Ekert PG, Pakusch M, et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 2000; 102:43–53.

    Article  PubMed  CAS  Google Scholar 

  43. Du CY, Fang M, Li YC, Li L, Wang XD. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 2000; 102:33–42.

    Article  PubMed  CAS  Google Scholar 

  44. Zou H, Li YC, Liu HS, Wang XD. An APAF-1 center dot cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem 1999;274:11,549–11,556.

    CAS  Google Scholar 

  45. Komatsu K, Miyashita T, Hang HY, et al. Human homologue of S-pombe Rad9 interacts with BCL-2/BCL-x(L) and promotes apoptosis. Nat Cell Biol 2000;2:1–6.

    Article  PubMed  CAS  Google Scholar 

  46. Nakano K, Vousden K. H. PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell 7: 683–694.

    Google Scholar 

  47. Liu XS, Kim CN, Yang J, Jemmerson R, Wang XD. Induction of apoptotic program in cell-free extracts: Requirement for dATP and cytochrome c. Cell 1996;86:147–157.

    Article  PubMed  CAS  Google Scholar 

  48. Kluck RM, BossyWetzel E, Green DR, Newmeyer DD. The release of cytochrome c from mitochondria: A primary site for Bcl-2 regulation of apoptosis. Science 1997;275:1132–1136.

    Article  PubMed  CAS  Google Scholar 

  49. Bodmer JL, Schneider P, Tschopp J. The molecular architecture of the TNF superfamily. Trend Biochem Sci 2002;27:19–26.

    Article  PubMed  CAS  Google Scholar 

  50. Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: Integrating mammalian biology. Cell 2001; 104:487–501.

    Article  PubMed  CAS  Google Scholar 

  51. Chen GQ, Goeddel DV. TNF-R1 signaling: A beautiful pathway. Science 2002;296:1634–1635.

    Article  PubMed  CAS  Google Scholar 

  52. Seol DW, Li JR, Seol MH, et al. Signaling events triggered by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL): Caspase-8 is required for TRAIL-induced apoptosis. Cancer Res 2001;61:1138–1143.

    PubMed  CAS  Google Scholar 

  53. Sprick MR, Rieser E, Stahl H, Grosse-Wilde A, Weigand MA, Walczak H. Caspase-10 is recruited to and activated at the native TRAIL and CD95 death-inducing signalling complexes in a FADD-dependent manner but can not functionally substitute caspase-8. EmMBO J 2002;21:4520–4530.

    Article  CAS  Google Scholar 

  54. Reed JC. Apoptosis-based therapies for neoplastic diseases. International J Hematol 2002;76:261.

    Google Scholar 

  55. Bian X, Giordano TD, Lin HJ, Solomon G, Castle VP, Opipari AW. Chemotherapy-induced apoptosis of S-type neuroblastoma cells requires caspase-9 and is augmented by CD95/Fas stimulation. J Biol Chem 2004;279:4663–4669.

    Article  PubMed  CAS  Google Scholar 

  56. Yang XH, Sladek TL, Liu XS, Butler BR, Froelich CJ, Thor AD. Reconstitution of caspase 3 sensitizes MCF-7 breast cancer cells to doxorubicin-and etoposide-induced apoptosis. Cancer Res 2001;61:348–354.

    PubMed  CAS  Google Scholar 

  57. Gu J, Kagawa S, Takakura M, et al. Tumor-specific transgene expression from the human telomerase reverse transcriptase promoter enables targeting of the therapeutic effects of the Bax gene to cancers. Cancer Res 2000;60:5359–5364.

    PubMed  CAS  Google Scholar 

  58. Pataer A, Smythe WR, Yu R, et al. Adenovirus-mediated Bak gene transfer induces apoptosis in mesothelioma cell lines. J Thor Cardiovasc Surg 2001;121:61–67.

    Article  CAS  Google Scholar 

  59. Naumann U, Schmidt F, Wick W, et al. Adenoviral natural born killer gene therapy for malignant glioma. Hum Gene Ther 2003;14:1235–1246.

    Article  PubMed  CAS  Google Scholar 

  60. Fukazawa T, Walter B, Owen-Schaub LB. Adenoviral bid overexpression induces caspase-dependent cleavage of truncated bid and p53-independent apoptosis in human non-small cell lung cancers. J Biol Chem 2003;278:25,428–25,434.

    Article  CAS  Google Scholar 

  61. Ehtesham M. Samoto K, Kabos P, et al. Treatment of intracranial glioma with in situ interferongamma and tumor necrosis factor-alpha gene transfer. Cancer Gene Ther 2002;9:925–934.

    Article  PubMed  CAS  Google Scholar 

  62. Shinoura N, Yamamoto N, Asai A, Kirino T, Hamada H. Adenovirus-mediated transfer of Fas ligand gene augments radiation-induced apoptosis in U-373MG glioma cells. Jap J Cancer Res 2000; 91:1044–1050.

    CAS  Google Scholar 

  63. Lin TY, Gu J, Zhang LD, et al. Targeted expression of green fluorescent protein/tumor necrosis factor-related apoptosis-inducing ligand fusion protein from human telomerase reverse transcriptase promoter elicits antitumor activity without toxic effects on primary human hepatocytes. Cancer Res 2002;62:3620–3625.

    PubMed  CAS  Google Scholar 

  64. Yamabe K, Shimizu S, Ito T, et al. Cancer gene therapy using a pro-apoptotic gene, caspase-3. Gene Ther 1999;6:1952–1959.

    Article  PubMed  CAS  Google Scholar 

  65. Marcelli M, Cunningham GR, Walkup M, et al. Signaling pathway activated during apoptosis of the prostate cancer cell line LNCaP: Overexpression of caspase-7 as a new gene therapy strategy for prostate cancer. Cancer Res 1999;59:382–390.

    PubMed  CAS  Google Scholar 

  66. Lin TY, Huang XF, Gu J, et al. Long-term tumor-free survival from treatment with the GFP-TRAIL fusion gene expressed from the hTERT promoter in breast cancer cells. Oncogene 2002;21: 8020–8028.

    Article  PubMed  CAS  Google Scholar 

  67. Voelkel-Johnson C, King DL, Norris JS. Resistance of prostate cancer cells to soluble TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) can be overcome by doxorubicin or adenoviral delivery of full-length TRAIL. Cancer Gene Ther 2002;9:164–172.

    Article  PubMed  CAS  Google Scholar 

  68. Armeanu S, Lauer UM, Smirnow I, et al. Adenoviral gene transfer of tumor necrosis factor-related apoptosis-inducing ligand overcomes an impaired response of hepatoma cells but causes severe apoptosis in primary human hepatocytes. Cancer Res 2003;63:2369–2372.

    PubMed  CAS  Google Scholar 

  69. Kagawa S, Gu J, Swisher SG, et al. Antitumor effect of adenovirus-mediated Bax gene transfer on p53-sensitive and p53-resistant cancer lines. Cancer Res 2000;60:1157–1161.

    PubMed  CAS  Google Scholar 

  70. Khan AU, Lal SK. Ribozymes: A modern tool in medicine. J Biomed Sci 2003; 10:457–467.

    Article  PubMed  CAS  Google Scholar 

  71. Yi HK, Nam SY, Kim JC, Kim JS, Lee DY, Hwang PH. Induction of apoptosis in K562 cells by dominant negative c-myb. Exper Hematol 2002;30:1139–1146.

    Article  CAS  Google Scholar 

  72. Rousselet N, Mills L, Jean D, Tellez C, Bar-Eli M, Frade R. Inhibition of tumorigenicity and metastasis of human melanoma cells by anti-cathepsin L single chain variable fragment. Cancer Res 2004;64:146–151.

    Article  PubMed  CAS  Google Scholar 

  73. Duggan BJ, Maxwell P, Kelly JD, et al. The effect of antisense Bcl-2 oligonucleotides on Bcl-2 protein expression and apoptosis in human bladder transitional cell carcinoma. J Urol 2001;166: 1098–1105.

    Article  PubMed  CAS  Google Scholar 

  74. Dillin A. The specifics of small interfering RNA specificity. Proc Natl Acad Sci U S A 2003;100: 6289–6291.

    Article  PubMed  CAS  Google Scholar 

  75. Futami T, Miyagishi M, Seki M, Taira K. Induction of apoptosis in HeLa cells with siRNA expression vector targeted against bcl-2. Nucleic Acids Res Suppl, 2002;251–252.

    Google Scholar 

  76. Ross DM, Hughes TP. Cancer treatment with kinase inhibitors: what have we learnt from imatinib? Br J Cancer 2004;90:12–19.

    Article  PubMed  CAS  Google Scholar 

  77. Kagawa S, Pearson SA, Ji L, et al. A binary adenoviral vector system for expressing high levels of the proapoptotic gene bax. Gene Ther 2000;7:75–79.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX

    Lidong Zhang MD, PhD

  2. Department of Thoracic and Cardiovascular Surgery-Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX

    Bingliang Fang MD, phD

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  1. Lidong Zhang MD, PhD
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  2. Bingliang Fang MD, phD
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Editors and Affiliations

  1. The University of Texas M. D. Anderson Cancer Center, Houston, TX

    Kelly K. Hunt MD  & Stephen G. Swisher MD  & 

  2. Inselspital Bern, University of Bern, Bern, Switzerland

    Stephan A. Vorburger MD, MCR

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© 2007 Humana Press Inc., Totowa, NJ

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Zhang, L., Fang, B. (2007). Oncogenes, Tumor Suppressor Genes and Apoptosis-Inducing Genes Utilized in Cancer Gene Therapy. In: Hunt, K.K., Vorburger, S.A., Swisher, S.G. (eds) Gene Therapy for Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-222-9_10

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  • DOI: https://doi.org/10.1007/978-1-59745-222-9_10

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-472-2

  • Online ISBN: 978-1-59745-222-9

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