Cytotechnology

, Volume 27, Issue 1–3, pp 283–292 | Cite as

The role of oncogenes in drug resistance

  • Dihua Yu
Article

Abstract

Increasing evidences indicate that oncogenes can directly or indirectly impact on cancer-cell drug resistance. This chapter provides a conceptual review regarding the role of oncogenes in drug resistance. The review is focused on drug resistance mediated by oncogenes encoding growth factor receptors, signaling molecules, transcription factors, cell-cycle regulators, and apoptosis regulators. It is my hope that better undertsnading on the role of oncogenes in drug resistance will invoke ideas on new approaches to enhance the cytotoxicity of the standard chemotherapeutic agents by functional perturbation of resistance-inducing oncogenes.

apoptosis cell-cycle control Growth factor receptors signal transduction transcription factors 

References

  1. Aboud-Pirak E, Hurwitz E, Pirak ME, Bellot F, Schlessinger J and Sela M (1988) Efficacy of antibodies to epidermal growth factor receptor against KB carcinoma in vitro and in nude mice. J Natl Cancer Inst 80: 1605-1611.Google Scholar
  2. Aggarwal BB, Totpal K, Ali-Osman F, Budde RJ and Pocsik E (1994) pp60v-src kinase overexpression leads to cellular resistance to the antiproliferative effects of tumor necrosis factor. FEBS Letters 345: 219-224.CrossRefGoogle Scholar
  3. Arteaga CL, Winnier AR, Poirier MC, Lopez-Larraza DM, Shawver LK, Hurd SD and Stewart SJ (1994) p185c-erbB-2 signaling enhances cisplatin-induced cytotoxicity in human breast carcinoma cells: association between an oncogenic receptor tyrosine kinase and drug-induced DNA repair. Cancer Res 54: 3758–3765.Google Scholar
  4. Bargmann CI, Hung M-C and Weinberg RA (1986) The neuoncogene encodes an epidermal growth factor receptor-related protein. Nature 319: 226-230.CrossRefGoogle Scholar
  5. Bartkova J, Lukas J, Muller H, Strauss M, Gusterson B and Bartek J (1995) Abnormal patterns of D-type cyclin expression and G1 regulation in human head and neck cancer. Cancer Research 55: 949-56.Google Scholar
  6. Bates S and Peters G (1995) Cyclin D1 as a cellular proto-oncogene. Seminars in Cancer Biology 6: 73-82.CrossRefGoogle Scholar
  7. Begleiter A, Mowat M, Israels LG and Johnston JB (1996) Chlorambucil in chronic lymphocytic leukemia: mechanism of action. Leukemia and Lymphoma 23: 187-201.Google Scholar
  8. Bhushan A, Abramson R, Chiu JF and Tritton TR (1992) Expression of c-fos in human and murine multidrug-resistant cells. Mol Pharm t42: 69-74.Google Scholar
  9. Carraway KL, Sliwkowski MX, Akita R, Platko JV, Guy PM, Nuijens A, Diamonti J, Vandelen RL, Cantley LC and Cerione RA (1994) The erbB-3 gene product is a receptor for heregulin. J Biol Chem 269: 14303-14306.Google Scholar
  10. Chang T, Khalsa O, Wang H, Lee ME and Schlegel R (1996) Staurosporine resistance accompanies DNA tumor virus-induced immortalization and is independent of the expression and activities of ERK1, ERK2, cyclin A, cyclin-dependent kinase (cdk)2, and cdk4. Cell Growth and Diff 7: 361-372.Google Scholar
  11. Chevalier B, Fumoleau P, Kerbrat P, Dieras V, Roche H, Krakowski I, Azli N, Bayssas M, Lentz MA and Van Glabbeke M (1995) Docetaxel is a major cytotoxic drug for the treatment of advanced breast cancer: a phase 2 trial of the clinical screening cooperative group of the European Organization for Research and Treatment of Cancer. J of Clin Oncol 13: 314-322.Google Scholar
  12. Chrysogelos SA and Dickson RB (1994) EGF receptor expression, regulation, and function in breast cancer. Breast Cancer Res and Treatment 29: 29-40.CrossRefGoogle Scholar
  13. Coussens L, Yang-Feng TL, Liao Y-C, Chen E, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U, Levinson A and Ullrich A (1985) Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neuoncogene. Science 230: 1132-1139.Google Scholar
  14. Dickstein B, Valverius EM, Wosikowski K, Saceda M, Pearson JW and Martin MB et al. (1993) Increased epidermal growth factor receptor in an estrogen-responsive, adriamycin-resistant MCF-7 cell line. J Cell Physiol 157.Google Scholar
  15. Dixit M, Yang JL, Poirier MC, Price JO, Andrews PA and Arteaga CL (1997) Abrogation of cisplatin-induced programmed cell death in human breast cancer cells by epidermal grwoth factor antisense RNA. J Natl Cancer Inst 89: 365-373.CrossRefGoogle Scholar
  16. Fan Z, Baselga B, Masui H and Mendelsohn J (1993) Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well-established A431 cell xenografts. Cancer Res 53: 4637-4642.Google Scholar
  17. Gillett C, Fanti V, Smith R, Fisher C, Bartek J, Dickson C, Barnes D and Peters G (1994) Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res 54.Google Scholar
  18. Graus-Porta D, Beerli RR, Daly JM and Hynes NE (1997) ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. The EMBO Journal 16: 1647-1655.CrossRefGoogle Scholar
  19. Gusterson BA, Gelber RD, Goldhirsch A, Price KN, Save-Soderborgh J, Anbazhagan R, Styles J, Rudenstam C-M, Golouh R, Reed R, Martinez-Tello F, Tiltman A, Torhorst J, Grigolato P, Bettelheim R, Neville AM, Burki K, Castiglione M, Collins J, Lindtner J, Senn H-J and Ludwig IBCSG (1992) Prognostic importance of c-erbB-2 expression in breast cancer. J Clin Oncol 10: 1049-1056.Google Scholar
  20. Hancock MC, Langton BC, Chan T, Toy P, Monahan JJ, Mischak RP and Shawver LK (1991) A monoclonal antibody against the c-erbB-2 protein enhances the cytotoxicity of cis-diamminedichloroplatinum against human breast and ovarian tumor cell lines. Cancer Res 51: 4575-4580.Google Scholar
  21. Hayes JD and Pulford DJ (1995) The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Critical Reviews in Biochemistry and Molecular Biology 30: 445-600.Google Scholar
  22. Hill ME, MacLennan KA, Cunningham DC, Vaughan-Hudson B, Burke M, Clarke P, Di Stefano F, Anderson L, Vaughan-Hudson G, Mason D, Selby P and Linch DC (1996) Prognostic significance of BCL-2 expression and bcl-2 major breakpoint region rearrangement in diffuse large cell non-Hodgkin's lymphoma: a British National Lymphoma Investigation Study. Blood 88: 1046-1051.Google Scholar
  23. Hochhauser D, Schnieders B, Ercikan-Abali E, Gorlick R, Muise-Helmericks R, Li WW, Fan J, Banerjee D and Bertino JR (1996) Effect of cyclin D1 overexpression on drug sensitivity in a human fibrosarcoma cell line. Journal of the National Cancer Institute 88: 1269-1275.Google Scholar
  24. Hockenbery D, Nunez G, Milliman C, Schreiber RD and Korsmeyer SJ (1990) Bcl-2 is an inner mitochodrial membrane protein that blocks programmed cell death. Nature 348: 334-336.CrossRefGoogle Scholar
  25. Hockenbery DM, Oltvai ZN, Yin X-M, Milliman C and Korsmeyer SJ (1993) Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75: 241-251.CrossRefGoogle Scholar
  26. Holmes FA, Walters RS, Theriault RL, Forman AD, Newton LK, Raber MN, Buzdar AU, Frye DK and Hortobagyi GN (1991) Phase II trial of Taxol, an active drug in the treatment of metastatic breast cancer. J Natl Cancer Inst 83: 1797-1805.Google Scholar
  27. Huang Y, Ibrado AM, Reed JC, Bullock G, Ray S, Tang C and Bhalla K (1997) Co-expression of several molecular mechanisms of multidrug resistance and their significance for paclitaxel cytotoxicity in human AML HL-60 cells. Leukemia 11: 253-257.CrossRefGoogle Scholar
  28. Jacquemier J, Penault-Llorca F, Viens P, Houvenaeghel G, Hassoun J, Torrente M, Adelaide J and Birnbaum D (1994) Breast cancer response to adjuvant chemotherapy in correlation with erbB2 and p53 expression. Anticancer Res 14: 2773-2778.Google Scholar
  29. Kitada S, Takayama S, De Riel K, Tanaka S and Reed JC (1994) Reversal of chemoresistance of lymphoma cells by antisense-mediated reduction of bcl-2 gene expression. Antisense Research and Development 4: 71-79.Google Scholar
  30. Kopnin BP, Stromskaya TP, Kondratov RV, Ossovskaya VS, Pugacheva EN, Rybalkina EY, Khokhlova OA and Chumakov PM (1995) Influence of exogenous ras and p53 on P-glycoprotein function in immortalized rodent fibroblasts. Oncology Research 7: 299-306.Google Scholar
  31. Livingstone A and Mairs RJ (1997) N-myc amplification and its relationship to experimental therapy. Journal of Neuro-Oncology 31: 33-39.CrossRefGoogle Scholar
  32. Marx J (1994) Oncogenes reach a milestone. Science 266: 1942-1944.Google Scholar
  33. Masumoto N and Nakano S (1997) Cell signaling and CDDP resistance. Japanese Journal of Cancer and Chemotherapy 24: 424-430.Google Scholar
  34. Mendelsohn J and Fan Z (1997) Epidermal Growth Factor Receptor Family and Chemosensitization. J Natl Cancer Inst 89: 341-343.CrossRefGoogle Scholar
  35. Mizutani Y, Fukumoto M, Bonavida B and Yoshida O (1994) Enhancement of sensitivity of urinary bladder tumor cells to cisplatin by c-myc antisense oligonucleotide. Cancer 74: 2546-2554.CrossRefGoogle Scholar
  36. Moffat GJ, McLaren AW and Wolf CR (1994) Involvement of Jun and Fos proteins in regulating transcriptional activation of the human pi class glutathione S-transferase gene in multidrug-resistant MCF7 breast cancer cells. J Biol Chem 269: 16397-16402.Google Scholar
  37. Morabito F, Filangeri M, Callea I, Sculli G, Callea V, Fracchiolla NS, Neri A and Brugiatelli M (1997) Bcl-2 protein expression and p53 gene mutation in chronic lymphocytic leukemia: correlation with in vitro sensitivity to chlorambucil and purine analogs. Haematologica 82: 16-20.Google Scholar
  38. Muss HB, Thor AD, Berry DA, Kute T, Liu ET, Koerner F, Cirrincione CT, Budman DR, Wood WC, Barcos M and Henderson IC (1994) C-erbB-2 expression and response to adjuvant therapy in woman with node-positive early breast cancer. N Engl J Med 330: 1260-1266.CrossRefGoogle Scholar
  39. Norris MD, Bordow SB, Marshall GM, Haber PS, Cohn SL and Haber M (1996) Expression of the gene for multidrug-resistance-associated protein and outcome in patients with neuroblastoma. N Engl J Med 334: 231-238.CrossRefGoogle Scholar
  40. Pietras RJ, Fendly BM, Chazin VR, Pegram MD, Howell SB and Slamon DJ (1994) Antibody to HER-2/neu receptor blocks DNA repair after cisplatin in human breast cancer and ovarian cancer cells. Oncogene 9: 1829-1838.Google Scholar
  41. Plowman GD, Grenn JM, Culouscou J-M, Carlton GW, Rothwell VM and Buckley S (1993) Heregulin induces tyrosine phosphorylation of HER4/p180erbB-4. Nature. 366: 473-475.CrossRefGoogle Scholar
  42. Ransone LJ and Verma IM (1990) Nuclear proto-oncogenes fos and jun. Annu Rev Cell Biol 6: 539-557.CrossRefGoogle Scholar
  43. Reed JC (1995) Bcl-2: preventino of apoptosis as a mechanism of drug resistance. Hematology - Oncology Clinics of North America 9: 451-473.Google Scholar
  44. Reeve JG, Xiong J, Morgan J and Bleehen NM (1996) Expression of apoptosis-regulatory genes in lung tumour cell lines: relationship to p53 expression and relevance to acquired drug resistance. British J of Cancer 73: 1193-1200.Google Scholar
  45. Riva C, el Khyari S, Rustum Y and Barra Y (1995) Resistance to cytosine arabinoside in cells transfected with activated Ha-ras oncogene. Anticancer Research 15: 1297-1302.Google Scholar
  46. Riva-Lavieille C (1994) Drug resistance, oncogenes and antioncogenes in epithelial tumors. Bulletin du Cancer 81: 105s-111s.Google Scholar
  47. Scanlon KJ, Ishida H and Kashani-Sabet M (1994) Ribozyme-mediated reversal of the multidrug-resistant phenotype. Proceedings of the National Academy of Sciences of the United States of America 91: 11123-11127.CrossRefGoogle Scholar
  48. Schechter AL, Hung M-C, Vaidyanathan L, Weinberg RA, Yang-Feng TL, Francke U, Ullrich A and Coussens L (1985) The neugene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science 229: 976-978.Google Scholar
  49. Sepp-Lorenzino L, Bos M, Ma Z, Baselga J, Rands E and Kohl NE et al. (1996) Farnesyl protein transferase inhibitors (FITs) block tyrosine kinase signal transduction and act in concert with an anti-EGF receptor antibody to inhibit cancer cell growth (Abstract). Proc Am Assoc Cancer Res 37: 421.Google Scholar
  50. Sklar MD and Prochownik EV (1991) Modulation of cis-platinum resistance in Friend erythroleukemia cells by c-myc. Cancer Research 51: 2118-2123.Google Scholar
  51. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A and McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neuoncogene. Science 235: 177-182.Google Scholar
  52. Sliwkowski MX, Schaefer G, Akita RW, Lofgren JA, Fitzpatrick VD, Nuijens A, Fendly BM, Cerione RA, Vandlen RL and Carraway KL (1994) Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin. J Biol Chem 269: 14661-14665.Google Scholar
  53. Stoetzer OJ, Nussler V, Darsow M, Gullis E, Pelka-Fleischer R, Scheel U and Wilmanns W(1996) Association of bcl-2, bax, bclxL and interleukin-1 beta-converting enzyme expression with initial response to chemotherapy in acute myeloid leukemia. Leukemia 10Suppl 3: S18-S22.Google Scholar
  54. Tang C, Willingham MC, Reed JC, Miyashita T, Ray S, Ponnathpur V, Huang Y, Mahoney ME, Bullock G and Bhalla K (1994) High levels of p26BCL-2 oncoprotein retard taxol-induced apoptosis in human pre-B leukemia cells. Leukemia 8: 1960-1969.Google Scholar
  55. Tanio Y (1992) Relationship between drug resistance and oncogenes in lung cancer cell lines. Nippon Kyobu Shikkan Gakkai Zasshi - Japanese Journal of Thoracic Diseases 30: 42-47.Google Scholar
  56. Teixeira C, Reed JC and Pratt MA (1995) Estrogen promotes chemotherapeutic drug resistance by a mechanism involving Bcl-2 proto-oncogene expression in human breast cancer cells. Cancer Research 55: 3902-3907.Google Scholar
  57. Tetu B and Brisson J (1994) Prognostic significance of HER-2/neu oncoprotein expression in node-positive breast cancer. The influence of the pattern of immunostaining and adjuvant therapy. Cancer 73: 2359-65.Google Scholar
  58. Theodorescu D, Connors KM, Groce A, Hoffman RM and Kerbel RS (1993) Lack of influence of c-Ha-ras expression on the drug sensitivity of human bladder cancer histocultured in three-dimensions. Anticancer Research. 13: 941-946.Google Scholar
  59. Tsai C-M, Chang K-T, Perng R-P, Mitsudomi T, Chen M-H, Kadoyama C and Gazdar AF (1993) Correlation of intrinsic chemoresistance of non-small-cell lung cancer cell lines with HER-2/neugene expression but not with rasgene mutation. J Natl Cancer Inst 85: 897-901.Google Scholar
  60. Tsai C-M, Yu D, Chang K-T, Wu L-H, Perng PR-P, Ibrahim NK and Hung M-C (1995) Enhanced chemoresistance by elevation of p185neulevels in HER-2/neutransfected human lung cancer cells. J Natl Cancer Inst 87: 682-684.Google Scholar
  61. Tsai CM, Levitzki A, Wu L-H, Chang KT, Chen C-C, Gazit A and Perng RP (1996) Enhancement of chemosensitivity by tyrphostin AG825 in high-p185neuexpressing non-small cell lung cancer cells. Cancer Res 56: 1068-1074.Google Scholar
  62. Van Waardenburg RC, Prins J, Meijer C, Uges DR, De Vries EG and Mulder NH (1996) Effects of c-myc oncogene modulation on drug resistance in human small cell lung carcinoma cell lines. Anticancer Research 16: 1963–1970.Google Scholar
  63. Vickers PJ, Dickson RB, Shoemaker R and Cowan KH (1988) A multidrug-resistant MCF-7 human breast cancer cell line which exhibits cross-resistance to antiestrogens and hormone-independent tumor growth in vivo. Mol Endocrinol 2: 886-892.CrossRefGoogle Scholar
  64. Walker A, Taylor ST, Hickman JA and Dive C (1997) Germinal center-derived signals act with Bcl-2 to decrease apoptosis and increase clonogenicity of drug-treated human B lymphoma cells. Cancer Research 57: 1939-1945.Google Scholar
  65. Wall ME and Wani MC (1995) Camptothecin and Taxol: Discovery to Clinic - Thirteenth Bruce F. Cain Memorial Award Lecture. Cancer Res 55: 753-760.Google Scholar
  66. Wallasch C, Weiss FU, Niederfellner G, Jallal B, Issing W and Ullrich A (1995) Heregulin-dependent regulation of HER2/neu oncogenic signaling by heterodimerization with HER3. EMBO Journal 14: 4267-4275.Google Scholar
  67. Wani MC, Taylor HL, Wall ME, Coggon P and McPhail AT (1971) Plant antitumor agents. VI. The isolation and structure of Taxol, a novel antileukemic and antitumor agent from Taxus Brevifolia. J Am Chem Soc 93: 2325-2327.CrossRefGoogle Scholar
  68. Wilson WH, Teruya-Feldstein J, Fest T, Harris C, Steinberg SM, Jaffe ES and Raffeld M (1997) Relationship of p53, bcl-2, and tumor proliferation to clinical drug resistance in non-Hodgkin's lymphomas. Blood 89: 601-609.Google Scholar
  69. Wood DP Jr, Anderson AE, Fair R and Chaganti RS (1992) Ras oncogene point mutations in bladder cancer resistant to cisplatin. Urological Research 20: 313-316.CrossRefGoogle Scholar
  70. Yamamoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N, Saito T and Toyoshima K (1986) Similarity of protein encoded by the human c-erbB-2 gene to epidermal growth factor. Nature 319: 230-234.CrossRefGoogle Scholar
  71. Yamazaki H, Schneider E, Myers CE and Sinha BK (1994) Oncogene overexpression and de novo drug-resistance in human prostate cancer cells. Biochimica et Biophysica Acta 1226: 89-96.Google Scholar
  72. Yarden Y and Weinberg RA (1989) Experimental approaches to hypothetical hormones: detection of a candidate ligand of the neu protooncogene. Proc Natl Acad Sci USA 86: 3179-3183.CrossRefGoogle Scholar
  73. Yu D, Liu B, Sun D, Jing T, Price JE, Singletary SE, Hortobagyi GN and Hung MC (1998) Overexpression of both p185c-erbB2 and p170mdr-1 renders breast cancer cells highly resistant to Taxol. Oncogene 16: 2087-2094.CrossRefGoogle Scholar
  74. Yu D, Liu B, Tan M, Li J, Wang S-S and Hung M-C (1996) Overexpression of c-erbB-2/neu in breast cancer cells confers increased resistance to Taxol via mdr-1-independent mechanisms. Oncogene 13: 1359-1365.Google Scholar
  75. Zhang L and Hung M-C (1996) Sensitization of HER-2/neuoverexpressing non-small cell lung cancer cells to chemotherapeutic drugs by tryosine kinase inhibitor emodin. Oncogene 12: 571-576.Google Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Dihua Yu
    • 1
  1. 1.Departments of Surgical Oncology and Tumor BiologyThe University of Texas, M.D. Anderson Cancer CenterHoustonU.S.A.

Personalised recommendations