Medical Oncology

, Volume 18, Issue 1, pp 3–14 | Cite as

Apoptosis and cell growth inhibition as antitumor effector functions of interferons

Review Article


Since their introduction to the clinic some 30 yr ago, interferons (IFNs) have become standard therapy for a range of disorders, including malignant and benign tumors as well as various viral diseases. Although IFNs will induce remissions in some patients with cancer, they are of no benefit or, at best, lead only to minor improvements in the great majority of patients with malignant disease. One of the great challenges of IFN research is to understand the multiple ways by which IFNs influence the behavior of tumor cells and to identify the factors that underlie the resistance of some tumors to IFNs. This reviews is written with a focus on two anticellular effects of IFN, inhibition of proliferation and induction of apoptosis, possible mechanisms underlying the antitumor action of IFN. In addition, possible reasons for IFN tumor cell resistance are also discussed.

Key Words

Interferons tumor cells resistance apoptosis cell cycle arrest 


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  1. 1.
    De Mayer, E. and De Mayer-Guiginard, J. (1998). Interferons and Other Regulatory Cytokines, Wiley, New York.Google Scholar
  2. 2.
    Ihle, J.N. (1996). STATs: signal transducers and activators of transcription. Cell 84:331–334.PubMedCrossRefGoogle Scholar
  3. 3.
    Strander, H. and Cantell, K. (1966). Production of interferon by human leukocytes in vitro. Ann. Med. Exp. Fenn. 44:265–273.PubMedGoogle Scholar
  4. 4.
    Einhorn, S. and Strander, H. (1993). Interferon treatments of human malignancies—a short review. Med. Oncol. Tumor Pharmacother. 10:25–29.PubMedGoogle Scholar
  5. 5.
    Grandér, D., Öberg, K., Lundqvist, M.L., Janson, E.T., Erksson, B. and Einhorn, S. (1990). Interferon-induced enhancement of 2′,5′ oligoadenylate synthetase in mid-gut carcinoid tumors. Lancet 336:337–339.PubMedCrossRefGoogle Scholar
  6. 6.
    Gresser, I., Maury, C. and Brouty-boyé, D. (1972). Mechansim of the antitumor effect of interferon in mice. Nature 239:167–168.PubMedCrossRefGoogle Scholar
  7. 7.
    Gresser, I., Kaido, T., Maury, C., Woodrow, D., Moss, J. and Belardelli, F. (1994). Interaction of IFNα/β with host cells essential to the early inhibition of Friend erythroleukemia visceral metastases in mice. Int. J. Cancer 57:604–611.PubMedCrossRefGoogle Scholar
  8. 8.
    Einhorn, S., Ahre, A., Blomgren, H., Johansson, B., Mellstedt, H. and Strander, H. (1982). Interferon and natural killer cell activity in multiple myeloma. Lack of correlation between interferon-induced enhancement of natural killer cell activity and clinical response to human interferon-α. Int. J. Cancer 30:167–172.PubMedCrossRefGoogle Scholar
  9. 9.
    Håkansson, A., Gustafsson, B., and Krysander, I. (1996). Tumour-infiltrating lymphocytes in malignant melanoma and response to interferon alpha treatment. Br. J. Cancer 74:670–676.PubMedGoogle Scholar
  10. 10.
    Grandér, D. (1998). How do mutated oncogenes and tumor suppressor genes cause cancer? Med. Oncol. 15:20–26.PubMedGoogle Scholar
  11. 11.
    Waldman, T., Zhang, Y. and Dillehay, L. (1997). Cell-cycle arrest versus cell death in cancer therapy. Nature Med. 3:1034–1036.PubMedCrossRefGoogle Scholar
  12. 12.
    Kerr, J.F., Wyllie, A.H. and Currie, A.R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26:239–257.Google Scholar
  13. 13.
    Kolenko, V.M., Uzzo, R. G., Bukowski, R. and Finke, J.H. (2000). Caspase-dependent and -independent death path-ways in cancer therapy. Apoptosis 5:17–20.PubMedCrossRefGoogle Scholar
  14. 14.
    Halestrap, A.P., Doran, E., Gillespie, J.P. and O’Toole, A. (2000) Mitochondria and cell death. Biochem. Soc. Trans. 28:170–177.PubMedGoogle Scholar
  15. 15.
    Nicholson, D.W. and Thornberry, N.A. (1997). Caspases: killer proteases. TIBS 22:299–306.PubMedGoogle Scholar
  16. 16.
    Wyllie, A.H. (1997). Apoptosis and cacinogenesis. Eur. J. Cell Biol. 73: 189–197.PubMedGoogle Scholar
  17. 17.
    Le, J., Yip, Y.K. and Vilcek, J. (1984). Cytolytic activity of interferon-gamma and its synergism with 5-fluorouracil. Int. J. Cancer. 34:495–500.PubMedCrossRefGoogle Scholar
  18. 18.
    Sangfelt, O., Erickson, S., Castro, J., Heiden, T., Einhorn, S. and Grander, D. (1997). Induction of apoptosis and inhibition of cell growth are independent responses to IFN-α. Cell Growth Diff. 8:343–352.PubMedGoogle Scholar
  19. 19.
    Grandér, D., Xu, B. and Einhorn, S. (1993). Cytotoxic effect of interferon on primary tumor cells. Studies in various malignancies. Eur. J. Cancer 14:1940–1943.CrossRefGoogle Scholar
  20. 20.
    Rodriguez-Villanueva, J. and Mcdonnell, T.J. (1995). Induction of apoptotic cell death in non-meanoma skin cancer by interferon-alpha. Int. J. Cancer 61:110–114.PubMedCrossRefGoogle Scholar
  21. 21.
    Deiss, L.P., Feinstein, E., Berissi, H., Cohen, O. and Kimchi, A. (1995). Identification of a novel serine/threonine kinase and a novel 15-kD protein as potential mediators of the γ interferon-induced cell death. Genes Dev. 9:15–30.PubMedCrossRefGoogle Scholar
  22. 22.
    Jewell, A.P., Worman, C.P., Lydyard, P.M., Yong, K.L., Giles, F.J. and Goldstone, A.H. (1994). Interferon-α up-regulates bcl-2 expression and protects B-CLL cells from apoptosis in vitro and in vivo. Br. J. Haematol. 88:268–274.PubMedGoogle Scholar
  23. 23.
    Milner, A.E., Grand, R.J. and Gregory, C.D. (1995). Effects of interferon-α on human B-cells: repression of apoptosis and prevention of cell growth are independent responses of Burkitt lymphoma cell lines. Int. J. Cancer 61:348–354.PubMedCrossRefGoogle Scholar
  24. 24.
    Liu, P., Oken, M., Van Ness, B. (1999). Interferon-alpha protects myeloma cell lines from dexamethosone-induced apoptosis. Leukemia 13: 473–480.PubMedCrossRefGoogle Scholar
  25. 25.
    Sangfelt, O., Einhorn, S., Björklund, A.C., Wiman K.G., Okan, I. and Grander, D. (1996). Wild-type p53-induced apoptosis in a Burkitt lymphoma cell line is inhibited by interferon-γ. Int. J. Cancer 67:106–112.PubMedCrossRefGoogle Scholar
  26. 26.
    Brenning, G., Jernberg, H., Gidlund, M., Sjöberg, O. and Nilsson, K. (1986). The effect of alpha and gamma-interferon on proliferation and production of IgE and beta 2-microglobulin in the human myeloma cell line U-266 and in an alpha-interferon resistant U-266 subline. Scand. J. Haematol. 37:280–288.PubMedGoogle Scholar
  27. 27.
    Taylor-Papadimitriou, J. and Rozengurt, E. (1985). Interferons as regulators of cell growth and differentiation, in Interferons, Their Impact in Biology and Medicine (J. Taylor-Papadimitriou, ed.), p. 81. Oxford Medical, Oxford.Google Scholar
  28. 28.
    Cuff, S. and Ruby, J. (1996). Evasion of apoptosis by DNA viruses. Immunol. Cell Biol. 74:527–537.PubMedCrossRefGoogle Scholar
  29. 29.
    Zhou, A., Paranjape, J., Brown, T.L., Nie, H., Naik, S., Dong B., et al. (1997). Interferon action and apoptosis are defective in mice devoid of 2′,5′-oligoadenylate-dependent RNase L. EMBO J. 16:6355–6363.PubMedCrossRefGoogle Scholar
  30. 30.
    Castelli, J.C., Hassel, B.A., Wood, K.A., Li, X.L., Amemiya, K., Dalakas, M.C., et al. (1997). A study of the interferon antiviral mechanism: Apoptosis activation by the 2–5A system. J. Exp. Med. 186:967–972.PubMedCrossRefGoogle Scholar
  31. 31.
    Lee, S.B. and Esteban, M. (1994). The interferon-induced double-stranded RNA-activated protein kinase induces apoptosis. Virology 199:491–496.PubMedCrossRefGoogle Scholar
  32. 32.
    Lee, S.B., Rodriguez, D., Rodriguez, J.R. and Esteban, M. (1997). The apoptosis pathway triggered by the interferon-induced protein protein kinase PKR requires the third basic domain, initiates upstream of Bcl-2, and involves ICE-like proteases. Virology 231:81–88.PubMedCrossRefGoogle Scholar
  33. 33.
    Tamura, T., Ishihara, M., Lamphier, M.S., Tanaka, N., Oishi, I., Aizawa, S., et al. (1995). An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitoge-activated T-lymphocytes. Nature 376:596–599.PubMedCrossRefGoogle Scholar
  34. 34.
    Kumar, A., Commane, M., Flickinger, T.W., Horvath, C.M. and Stark, G.R. (1997). Defective TNF-α-induced apoptosis in STAT1-null cells due to low constitutive levels of caspases. Science 278:1630–1632.PubMedCrossRefGoogle Scholar
  35. 35.
    Nagata, S. (1997). Apoptosis by death factor. Cell 88:355–365.PubMedCrossRefGoogle Scholar
  36. 36.
    Selleri, C., Sato, T., Del Vecchio, L., Luciano, L., Barrett, A.J., Rotoli, B., et al. (1997). Involvement of Fas-mediated apoptosis in the inhibitory effects of interferon-α in chronic myelogenous leukemia. Blood 89:957–964.PubMedGoogle Scholar
  37. 37.
    Dai, C.H., Price, J.O., Brunner, T. and Krantz, S.B. (1998). Fas ligand is present in human erythroid colony-forming cells and interacts with Fas induced by interferon γ to produce erythroid cell apoptosis. Blood 91:1235–1242.PubMedGoogle Scholar
  38. 38.
    Spets, H., Georgii-Hemming, P., Siljason, J., Nilsson, K. and Jernberg-Wiklund, H. (1998). Fas/APO-1 (CD95)-mediated apoptosis is activated by interferon-gamma and interferon-alpha in interleukin 6 (IL-6)-dependent cel IL-6-independent multiple myeloma cell lines. Blood 92:2914–2923.PubMedGoogle Scholar
  39. 39.
    Dai, C.H. and Sanford, B.K. (1999). Interferon γ induces upregulation and activation of caspases 1, 3, and 8 to produce apoptosis in human erythroid progenitor cells. Blood 93:3309–3316.PubMedGoogle Scholar
  40. 40.
    Deiss, L.P. and Kimchi, A. (1991). A genetic tool used to identify thioredoxin as a mediator of a growth inhibitory signal. Science 252:117–120.PubMedCrossRefGoogle Scholar
  41. 41.
    Cohen, O., Feinstein, E. and Kimchi, A. (1997). DAP-kinase is a Ca2+/calmodulin-dependent, cytoskeletal-associated protein kinase, with cell death-inducing functions that depend on its catalytic activity. EMBO J. 16:998–1008.PubMedCrossRefGoogle Scholar
  42. 42.
    Inbal, B., Cohen, O., Polak-Charcon, S., Kopolovic, J., Vadai, E., Eisenbach, L., et al. (1997). DAP kinase links the control of apoptosis to metastasis. Nature 390:180–184.PubMedCrossRefGoogle Scholar
  43. 43.
    Cohen, O., Inbal, B., Kissil, J.L., Raveh, T., Berissi, H., Spivak-Kroizaman, T., et al. (1999). DAP-kinase participates in TNF-alpha-and Fas-induced apoptosis and its function requires the death domain. J. Cell Biol. 146:141–148.PubMedGoogle Scholar
  44. 44.
    Haas-Kogan, D.A., Kogan, S.C., Levi, D., Dazin, P., T’Ang, A., Fung, Y.K., et al. (1995). Inhibition of apoptosis by the retinoblastoma gene product. EMBO J. 14:461–472.PubMedGoogle Scholar
  45. 45.
    Evan, G.I., et al. (1992). Induction of apoptosis in fibroblasts Myc-myc protein. Cell 69:119–128.PubMedCrossRefGoogle Scholar
  46. 46.
    Berry, D.E., Lu, Y., Schmidt, B., Fallon, P.G., O’Connell, C., Hu, S.X., et al. (1996). Retinoblastoma protein inhibits IFN-gamma induced apoptosis. Oncogene 12:1809–1819.PubMedGoogle Scholar
  47. 47.
    Pardee, A.B. (1974). A restriction point for control of normal animal cell proliferation. Proc. Natl. Acad. Sci. USA 71:1286–1290.PubMedCrossRefGoogle Scholar
  48. 48.
    Grana, X. and Reddy, E.P. (1995). Cell cycle control in mammalian cells: role of cyclin, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 11:211–219.PubMedGoogle Scholar
  49. 49.
    Morgan, D.O. (1995). Principles of CDK regulation. Nature 374:131–134.PubMedCrossRefGoogle Scholar
  50. 50.
    Sherr, C.J. and Roberts, J.M. (1995). Inhibitors of mammalian G1-cyclin-dependent kinases. Genes Dev. 9:1149–1163.PubMedCrossRefGoogle Scholar
  51. 51.
    Nevins, J.R. (1992). E2F: A link between the Rb tumor suppressor protein and viral oncoproteins. Science 258:424–429.PubMedCrossRefGoogle Scholar
  52. 52.
    Paucker, G., Cantell, K. and Henle, W. (1962). Quantitative studies on viral interference in suspended L cells III. Effect of interfering viruses and interferon on the growth rate of cells. Virology 17:324–334.PubMedCrossRefGoogle Scholar
  53. 53.
    Brenning, G., Åhre, A. and Nilsson, K. (1985). Correlation between in vitro and in vivo sensitivity to human leukocyte interferon in patients with multiple myeloma. Scand. J. Haematol. 35:543–549.PubMedCrossRefGoogle Scholar
  54. 54.
    Heyman, M., Grander, D., Bröndum-Nielsen, K., Cederblad, B., Liu, Y., Xu, B., et al. (1994). Interferon system defects in malignant T-cells. Leukemia 8:425–434.PubMedGoogle Scholar
  55. 55.
    Roos, G., Leanderson, T. and Lundgren, E. (1984). Interferoninduced cell cycle changes in human hematopoietic cell lines and fresh leukemic cells. Cancer Res. 44:2358–2362.PubMedGoogle Scholar
  56. 56.
    Balkwill, F. and Taylor-Papdimitriou, J. (1978). Interferon affects both G1 and S+G2 in cells stimulated from quiescence to growth. Nature 274:798–800.PubMedCrossRefGoogle Scholar
  57. 57.
    Tiefenbrun, N., Melamed, D., Levy, N., Resnitzky, D., Hoffman, I., Reed, S.I., et al. (1996). Alpha interferon suppresses the cyclin D3 and Cdc25A genes, leading to a reversible G0-like arrest. Mol. Cell. Biol. 16:3934–3944.PubMedGoogle Scholar
  58. 58.
    Sangfelt, O., Erickson, S., Castro, J., Heiden, T., Gustafsson, A., Einhorn, S., et al. (1999). Molecular mechansims underlying interferon-α-induced G0/G1 arrest: CKI-mediated regulation of G1 Cdk-complex and activation of pocket proteins. Oncogene 18:2798–2810.PubMedCrossRefGoogle Scholar
  59. 59.
    Kimchi, A. (1992). Cytokine triggered molecular pathways that control cell cycle arrest. J. Cell Biochem. 50:1–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Thomas, N.S., Pizzey, A.R., Tiwari, S., Williams, C.D. and Yang, J. (1998). p130, p107, and pRb are differentially regulated in proliferating cells and during the cell cycle arrest by alpha-interferon. J. Biol. Chem. 273:23,659–23,667.Google Scholar
  61. 61.
    Furukawa, Y., Iwase, S., Kikuchi, J., Nakamura, M., Yamada, H. and Matsuda, M. (1999). Transcriptional repression of the E2F-1 gene by interferon-alpha is mediated through induction of E2F-4/pRb and E2F-4/p130 complexes. Oncogene 18:2003–2014.PubMedCrossRefGoogle Scholar
  62. 62.
    Sangfelt, O., Erickson, S., Einhorn, S. and Grander, D. (1997). Induction of Cip/Kip and Ink4 cyclin dependent kinase inhibitors by interferon-α in hematopoietic cell lines. Oncogene 14:415–423.PubMedCrossRefGoogle Scholar
  63. 63.
    Hobeika, A.C., Subramaniam, P.S. and Johnson, H.M. IFN-alpha induces the expression of the cyclin-dependent kinase inhibitor p21 in human prostate cancer cells. Oncogene 14:1165–1170.Google Scholar
  64. 64.
    Harvat, B.L., Seth, P. and Jetten, A.M. (1997). The role of p27Kip1 in gamma interferon-mediated growth arrest of mammary epithelial cells and related defects in mammary carcinoma cells. Oncogene 17:2111–2122.CrossRefGoogle Scholar
  65. 65.
    Mandal, M., Bandyopadhyay, D., Goepfert, T.M. and Kumar, R. (1998). Interferon-alpha induces expression of cyclin-dependent kinase inhibitors p21WAF1 and p27KIP1 that prevent activation of cyclin-dependent kinase by CDK-activating kinase (CAK). Oncogene 16:217–225.PubMedCrossRefGoogle Scholar
  66. 66.
    Matsoka, M., Kenzaburo, T. and Shigetaka, A. (1998). Interferon-alpha-induced G1 phase arrest through up-regulated expression of CDK inhibitors p19Ink4D and p21Cip1 in mouse macrophages. Oncogene 16:2075–2086.CrossRefGoogle Scholar
  67. 67.
    Polyak, K., Kato, J.Y., Solomon, M.J., Sherr, C.J., Massague, J., Roberts, J.M., et al. (1994). p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest. Genes Dev. 8:9–22.PubMedCrossRefGoogle Scholar
  68. 68.
    Kato, J.Y., Matsuoka, M., Polyak, K., Massague, J. and Sherr, C.J. (1994). Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27Kip1) of cyclin-dependent kinase 4 activation. Cell 79:487–496.PubMedCrossRefGoogle Scholar
  69. 69.
    Chin, Y.E., Kitagawa, M., Su, W.C., You, Z.H., Iwamoto, Y. and Fu, X.Y. (1996). Cell growth arrest and induction of cyclin-dependent kinase inhibitor p21WAF1/CIP1 mediated by STAT1. Science 272:719–722.PubMedCrossRefGoogle Scholar
  70. 70.
    Bromberg, J.F., Horvath, C.M., Wen, Z., Schreiber, R.D. and Darnell, J.E., Jr. (1996). Transcriptionally active STAT1 is required for the antiproliferative effects of both interferon alpha and interferon gamma. Proc. Natl. Acad. Sci. USA 93:7673–7678.PubMedCrossRefGoogle Scholar
  71. 71.
    Ward, A.C., Touw, I. and Yoshimura, A. (2000). The JAKSTAT pathway in normal and perturbed hematopoiesis. Blood 95:19–29.PubMedGoogle Scholar
  72. 72.
    Yamaoka, T., Yano, M., Idehara, C., Yamada, T., Tomonari, S., Moritani, M., et al. (1999). Apoptosis and remodeling of beta cells by paracrine interferon-gamma without insulitis in transgenic mice. Diabetologia 42:566–573.PubMedCrossRefGoogle Scholar
  73. 73.
    Xaus, J., Cardo, M., Valledor, A.F., Soler, C., Lloberas, J. and Celada, A. (1999). Interferon gamma induces the expression of p21 waf1 and arrests macrophage cell cycle, preventing induction of apoptosis. Immunity 11:103–113.PubMedCrossRefGoogle Scholar
  74. 74.
    Chong, K.L., Feng, L., Schappert, K., Meurs, E., Donahue, T.F., Friesen, J.D., et al. (1992). Human p68 kinase exhibits growth suppression in yeast and homology to the translational regulator GCN2. EMBO J. 11:1553–1562.PubMedGoogle Scholar
  75. 75.
    Salzberg, S., Wreschner, D.H., Oberman, F., Panet, A. and Bakhanashvili, M. (1983). Isolation and characterization of an interferon-resistant cell line deficient in the induction of (2′,5′) oligoadenylate synthetase activity. Mol. Cell. Biol. 3:1759–1765.PubMedGoogle Scholar
  76. 76.
    Hassel, B.A., Zhou, A., Sotomayor, C., Maran, A. and Silverman, R.H. (1993). A dominant negative mutant of 2–5-A-dependent RNaseL suppresses antiproliferative and antiviral effects of interferon. EMBO J. 12:3297–3304.PubMedGoogle Scholar
  77. 77.
    Kirchhoff, S., Koromilas, A.E., Schaper, F., Grashoff, M., Sonenberg, N. and Hauser, H. (1995). IRF-1 induced cell growth inhibition and interferon induction requires the activity of the protein kinase PKR. Oncogene 11:439–445.PubMedGoogle Scholar
  78. 78.
    Gutterman, J.U. and Choubey, D. (1999). Retardation of cell proliferation after expression of p202 accompanies an increaase in p21 (WAF1/CIP1). Cell Growth Diff. 2:93–100.Google Scholar
  79. 79.
    Einat, M., Resnitzky, D. and Kimchi, A. (1985). Inhibitory effects of interferon on the experssion of genes regulated by platelet-derived growth factor. Proc. Natl. Acad. Sci. USA 82:7608–7612.PubMedCrossRefGoogle Scholar
  80. 80.
    Erickson, S., Sangfelt, O., Castro, J., Heyman, M., Einhorn, S. and Grander, D. (1999). Interferon-alpha inhibits proliferation in human T-lymphocytes by abrogation of IL-2 induced changes in cell cycle regulatory proteins. Cell Growth Diff. 10:575–582.PubMedGoogle Scholar
  81. 81.
    Sachindler, C. (1999). Cytokines and JAK-STAT signaling. Exp. Cell Res. 253:7–14.CrossRefGoogle Scholar
  82. 82.
    Marshall, M.S. (1995). Ras target proteins in eukarotic cells. FASEB J. 9:1311–1318.PubMedGoogle Scholar
  83. 83.
    Stark, G.R., Kerr, I.M., Williams, B.R.G., Silverman, R.H. and Schreiber, R.D. (1998). How cells respond to interferons. Annu. Rev. Biochem. 67:227–264.PubMedCrossRefGoogle Scholar
  84. 84.
    Sangfelt, O., Österborg, A., Grander, D., Anderbring, E., Öst, A., Mellstedt, H., et al. (1995). Response to interferon therapy in patients with multiple myeloma correlates with expression of the Bcl-2 oncoprotein. Int. J. Cancer 63:190–192.PubMedCrossRefGoogle Scholar
  85. 85.
    Haus, O. (2000). The genes of interferons and interferonrelated factors: localization and relationships with chromosome abberations in cancer. Arch. Immunol. Ther. Exp. 48:95–100.Google Scholar
  86. 86.
    Xu, B., Grander, D., Sangfelt, O. and Einhorn, S. (1994). Primary leukemia cells resistant to IFN-α in vitro are defective in the activation of the DNA-binding factor interferon-stimulated gene factor 3. Blood 84:1942–1949.PubMedGoogle Scholar
  87. 87.
    Wong, L.H., Krauer, K.G., Hatzinisiriou, I., Estcourt, M.J., Hersey, P., Tam, N.D., et al. (1997). Interferon-resistant human melanoma cells are deficient in ISGF3 components. STAT1, STAT2, and p48-ISGF3γ. J. Biol. Chem. 272:28,779–28,785.Google Scholar
  88. 88.
    Sun, W.H., Pabon, C., Alsayed, Y., Huang, P.P., Jandeska, S., Uddin, S., et al. (1998). Interferon-α resistance in a cutaneous T-cell lymphoma cell line is associated with lack of STAT1 expression. Blood 91:570–576.PubMedGoogle Scholar
  89. 89.
    Petricoin, E., David, M., Fang, H., Grimley, P., Larner, A.C. and Vande Pol, S. (1994). Human cancer cell lines express a negative transcriptional regulator of the interferon regulatory factor family of DNA binding proteins. Mol. Cell. Biol. 14:1477–1486.PubMedGoogle Scholar
  90. 90.
    Nelson, N., Marks, M.S., Driggers, P.H. and Ozato, K. (1993). Interferon consensus sequence-binding protein, a member of the interferon regulatory factor family, suppresses interferon-induced gene transcription. Mol. Cell. Biol. 13:588–599.PubMedGoogle Scholar
  91. 91.
    Sakamoto, H., Yasukawa, H., Masuhara, M., Tanimura, S., Sasaki, A., Yuge, K., et al. (1998). A Janus kinase inhibitor, JAB, is an interferon-γ inducible gene and confers resistance to interferons. Blood 92:1668–1676.PubMedGoogle Scholar
  92. 92.
    Rosenblum, M.G., Maxwell, B.L., Talpaz, M., Kelleher, P.J., McCredie, K.B. and Gutterman, J.U. (1986). In vivo sensitivity and resistance of CML cells to IFN-α: correlation with receptor binding and induction of 2′,5′-oligoadenylate synthetase. Cancer Res. 46:4848–4852.PubMedGoogle Scholar
  93. 93.
    Heyman, M., Nordgren, A., Jeddi-Tehrani, M., Rasool, O., Liu, Y., Grander, D, et al. (1996). A T-cell acute lymphocytic leukemia patient with two malignant cell populations carrying different deletions of the p16INK4 gene. Response to interferon-α therapy in one of the subclones. Leukemia 10:909–924.PubMedGoogle Scholar
  94. 94.
    Foster, G.R. and Finter, N.B. (1998). Are all type I human interferons equivalent? J. Viral Hepat. 5:143–152PubMedCrossRefGoogle Scholar
  95. 95.
    Grandér, D., Sangfelt, O. and Erickson, S. (1997). How does interferon exert its cell growth inhibitory effect? Eur. J. Haematol. 59:129–135.PubMedCrossRefGoogle Scholar

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© Humana Press Inc 2001

Authors and Affiliations

  1. 1.Research Laboratory of Radiumhemment, CCK, R8:03Karolinska HospitalStockholmSweden

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