Molecular Mechanisms of ErbB2-Mediated Breast Cancer Chemoresistance

  • Ming Tan
  • Dihua Yu
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 608)


The erbB2 (also known as HER2 or neu) gene encodes a 185-kDa transmembrane glycoprotein, which belongs to the epidermal growth factor receptor (EGFR) family. ErbB2 is a receptor tyrosine kinase with intrinsic tyrosine kinase activity. The mammalian EGFR family comprises four receptors (EGFR, ErbB2, ErbB3, and ErbB4), which are derived from a series of gene duplications early in vertebrate evolution and are 40%–45% identical.1 ErbB2 is the only EGFR family member for which no ligand has been found. This may be explained by the unique structure of the ErbB2 extracellular domain, which is not favorable for ligand binding.2,3 Since ErbB2 extracellular domain is always in the open conformation, ErbB2 is the preferred binding partner of all ErbB receptors even as a monomer.2, 3, 4 The binding of ErbB2 to other ErbB receptors results in increased signaling potency of the dimerized receptors through several means, including increased ligand affinity, increased coupling efficiency to signaling molecules, and decreased rate of receptor internalization.5, 6, 7, 8


Breast Cancer Breast Cancer Cell Metastatic Breast Cancer ErbB Receptor ErbB2 Protein 
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  1. 1.
    Stein RA, Staros JV. Evolutionary analysis of the ErbB receptor and ligand families. J Mol Evol 2000; 50(5):397–412.PubMedGoogle Scholar
  2. 2.
    Cho HS, Mason K, Ramyar KX et al. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 2003; 421(6924):756–760.CrossRefGoogle Scholar
  3. 3.
    Garrett TP, McKern NM, Lou M et al. The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors. Mol Cell 2003; 11(2):495–505.CrossRefPubMedGoogle Scholar
  4. 4.
    Graus-Porta D, Beerli RR, Daly JM et al. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J 1997; 16:1647–1655.CrossRefPubMedGoogle Scholar
  5. 5.
    Pinkas-Kramarski R, Soussan L, Waterman H et al. Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions. EMBO J 1996; 15:2452–2467.PubMedGoogle Scholar
  6. 6.
    Riese IInd DJ, van Raaij TM, Plowman GD et al. The cellular response to neuregulins is governed by complex interactions of the erbB receptor family. Mol Cell Biol 1995; 15(10):5770–5776.PubMedGoogle Scholar
  7. 7.
    Karunagaran D, Tzahar E, Beerli RR et al. ErbB-2 is a common auxiliary subunit of NDF and EGF receptors: Implications for breast cancer. EMBO J 1996; 15:254–264.PubMedGoogle Scholar
  8. 8.
    Jones JT, Akita RW, Sliwkowski MX. Binding specificities and affinities of egf domains for ErbB receptors. FEBS Lett 1999; 447(2–3):227–231.CrossRefPubMedGoogle Scholar
  9. 9.
    Slamon DJ, Godolphin W, Jones LA et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989; 244(4905):707–712.CrossRefPubMedGoogle Scholar
  10. 10.
    Lemoine NR, Jain S, Silvestre F et al. Amplification and overexpression of the EGF receptor and c-erbB-2 proto-oncogenes in human stomach cancer. Br J Cancer 1991; 64(1):79–83.PubMedGoogle Scholar
  11. 11.
    Sauter G, Moch H, Moore D et al. Heterogeneity of erbB-2 gene amplification in bladder cancer. Cancer Res 1993; 53(10 uppl):2199–2203.PubMedGoogle Scholar
  12. 12.
    Stenman G, Sandros J, Nordkvist A et al. Expression of the ERBB2 protein in benign and malignant salivary gland tumors. Genes Chromosomes Cancer 1991; 3(2):128–135.CrossRefPubMedGoogle Scholar
  13. 13.
    Tateishi M, Ishida T, Mitsudomi T et al. Prognostic value of c-erbB-2 protein expression in human lung adenocarcinoma and squamous cell carcinoma. Eur J Cancer 1991; 27(11):1372–1375.CrossRefPubMedGoogle Scholar
  14. 14.
    Hung M-C, Schechter AL, Chevray P-YM et al. Molecular cloning of the neu gene: absence of gross structural alteration in oncogenic alleles. Proc Natl Acad Sci USA 1986; 83:261–264.CrossRefPubMedGoogle Scholar
  15. 15.
    Tan M, Yao J, Yu D. Overexpression of the c-erbB-2 gene enhanced intrinsic metastatic potential in human breast cancer cells without increasing their transformation abilities. Cancer Res 1997; 57:1199–1205.PubMedGoogle Scholar
  16. 16.
    Moody SE, Sarkisian CJ, Hahn KT et al. Conditional activation of Neu in the mammary epithelium of transgenic mice results in reversible pulmonary metastasis. Cancer Cell 2002; 2(6):451–461.CrossRefPubMedGoogle Scholar
  17. 17.
    Holbro T, Civenni G, Hynes NE. The ErbB receptors and their role in cancer progression. Exp Cell Res 2003; 284(1):99–110.CrossRefPubMedGoogle Scholar
  18. 18.
    Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001; 2(2):127–137.CrossRefPubMedGoogle Scholar
  19. 19.
    Shawver LK, Slamon D, Ullrich A. Smart drugs: Tyrosine kinase inhibitors in cancer therapy. Cancer Cell 2002; 1(2):117–123.CrossRefPubMedGoogle Scholar
  20. 20.
    Carter P, Presta L, Gorman CM et al. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci USA 1992; 89(10):4285–4289.CrossRefPubMedGoogle Scholar
  21. 21.
    Pegram MD, Lipton A, Hayes DF et al. Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol 1998; 16(8):2659–2671.PubMedGoogle Scholar
  22. 22.
    Dickman S. Antibodies stage a comeback in cancer treatment. Science 1998; 280:1196–1197.CrossRefPubMedGoogle Scholar
  23. 23.
    Hortobagyi GN, Ueno NT, Xia W et al. Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: A phase I clinical trial. J Clin Oncol 2001; 19(14):3422–3433.PubMedGoogle Scholar
  24. 24.
    Madhusudan S, Tamir A, Bates N et al. A multicenter Phase I gene therapy clinical trial involving intraperitoneal administration of E1A-lipid complex in patients with recurrent epithelial ovarian cancer overexpressing HER-2/neu oncogene. Clin Cancer Res 2004; 10(9):2986–2996.CrossRefPubMedGoogle Scholar
  25. 25.
    Alvarez RD, Barnes MN, Gomez-Navarro J et al. A cancer gene therapy approach utilizing an anti-erbB-2 single-chain antibody-encoding adenovirus (AD21): A phase I trial. Clin Cancer Res 2000; 6(8):3081–3087.PubMedGoogle Scholar
  26. 26.
    Azemar M, Djahansouzi S, Jager E et al. Regression of cutaneous tumor lesions in patients intratumorally injected with a recombinant single-chain antibody-toxin targeted to ErbB2/HER2. Breast Cancer Res Treat 2003; 82(3):155–164.CrossRefPubMedGoogle Scholar
  27. 27.
    Rabindran SK, Discafani CM, Rosfjord EC et al. Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res 2004; 64(11):3958–3965.CrossRefPubMedGoogle Scholar
  28. 28.
    Buchholz TA, Hunt KK, Whitman GJ et al. Neoadjuvant chemotherapy for breast carcinoma: Multidisciplinary considerations of benefits and risks. Cancer 2003; 98(6):1150–1160.CrossRefPubMedGoogle Scholar
  29. 29.
    Allred DC, Clark GM, Tandon AK et al. Her-2/neu in node-negative breast, cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma. J Clin Oncol 1992; 10:599–605.PubMedGoogle Scholar
  30. 30.
    Gusterson BA, Gelber RD, Goldhirsch A et al. Prognostic importance of c-erbB-2 expression in breast cancer. J Clin Oncol 1992; 10(7):1049–1056.PubMedGoogle Scholar
  31. 31.
    Jarvinen TA, Holli K, Kuukasjarvi T et al. Predictive value of topoisomerase II alpha and other prognostic factors for epirubicin chemotherapy in advanced breast cancer. Br J Cancer 1998; 77:2267–2273.PubMedGoogle Scholar
  32. 32.
    Giani C, Finocchiaro G. Mutation rate of the CDKN2 gene in malignant gliomas. Cancer Res 1994; 54(24):6338–6339.PubMedGoogle Scholar
  33. 33.
    Fehm T, Maimonis P, Katalinic A et al. The prognostic significance of c-erbB-2 serum protein in metastatic breast cancer. Oncology 1998; 55:33–38.CrossRefPubMedGoogle Scholar
  34. 34.
    Colomer R, Montero S, Lluch A et al. Circulating HER2 extracellular domain and resistance to chemotherapy in advanced breast cancer. Clin Cancer Res 2000; 6:2356–2362.PubMedGoogle Scholar
  35. 35.
    Classen S, Kopp R, Possinger K et al. Clinical relevance of soluble c-erbB-2 for patients with metastatic breast cancer predicting the response to second-line hormone or chemotherapy. Tumour Biol 2002; 23(2):70–75.CrossRefPubMedGoogle Scholar
  36. 36.
    Colomer R, Llombart-Cussac A, Lluch A et al. Biweekly paclitaxel plus gemcitabine in advanced breast cancer: Phase II trial and predictive value of HER2 extracellular domain. Ann Oncol 2004; 15(2):201–206.CrossRefPubMedGoogle Scholar
  37. 37.
    Slamon DJ, Leyland-Jones B, Shak S et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344(11):783–792.CrossRefPubMedGoogle Scholar
  38. 38.
    Extra JM, Cognetti F, Chan S et al. First-line trastuzumab (Herceptin’) plus docetaxel versus docetaxel alone in women with HER2-positive metastatic breast cancer (MBC): Results from a randomised phase II trial (M77001). Br Cancer Res Treat 2003; 82(suppl 1):S47.Google Scholar
  39. 39.
    Yu D, Liu B, Jing T et al. Overexpression of both p185c-erbB2 and p170mdr-1 renders breast cancer cells highly resistant to taxol. Oncogene 1998; 16(16):2087–2094.CrossRefPubMedGoogle Scholar
  40. 40.
    Sellappan S, Grijalva R, Zhou X et al. Lineage infidelity of MDA-MB-435 cells: Expression of melanocyte proteins in a breast cancer cell line. Cancer Res 2004; 64(10):3479–3485.CrossRefPubMedGoogle Scholar
  41. 41.
    Yu D, Liu B, Tan M et al. Overexpression of c-erbB-2/neu in breast cancer cells confers increased resistance to Taxol via mdr-1-independent mechanisms. Oncogene 1996; 13:1359–1365.PubMedGoogle Scholar
  42. 42.
    Sabbatini AR, Basolo F, Valentini P et al. Induction of multidrug resistance (MDR) by transfection of MCF-10A cell line with c-Ha-ras and c-erbB-2 oncogenes. Int J Cancer 1994; 59(2):208–211.CrossRefPubMedGoogle Scholar
  43. 43.
    Ciardiello F, Caputo R, Pomatico G et al. Resistance to taxanes is induced by c-erbB-2 overexpression in human MCF-10A mammary epithelial cells and is blocked by combined treatment with an antisense oligonucleotide targeting type I protein kinase A. Int J Cancer 2000; 85(5):710–715.CrossRefPubMedGoogle Scholar
  44. 44.
    Chen X, Yeung TK, Wang Z. Enhanced drug resistance in cells coexpressing ErbB2 with EGF receptor or ErbB3. Biochem Biophys Res Commun 2000; 277(3):757–763.CrossRefPubMedGoogle Scholar
  45. 45.
    Witters LM, Santala SM, Engle L et al. Decreased response to paclitaxel versus docetaxel in HER-2/neu transfected human breast cancer cells. Am J Clin Oncol 2003; 26(1):50–54.CrossRefPubMedGoogle Scholar
  46. 46.
    Knuefermann C, Lu Y, Liu B et al. HER2/PI-3K/Akt activation leads to a multidrug resistance in human breast adenocarcinoma cells. Oncogene 2003; 22(21):3205–3212.CrossRefPubMedGoogle Scholar
  47. 47.
    Tanabe K, Kim R, Inoue H et al. Antisense Bcl-2 and HER-2 oligonucleotide treatment of breast cancer cells enhances their sensitivity to anticancer drugs. Int J Oncol 2003; 22(4):875–881.PubMedGoogle Scholar
  48. 48.
    Baselga J, Norton L, Albanell J et al. Recombinant humanized anti-HER2 antibody (Herceptin®) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res 1998; 58:2825–2831.PubMedGoogle Scholar
  49. 49.
    Lee S, Yang W, Lan KH et al. Enhanced sensitization to taxol-induced apoptosis by herceptin pretreatment in ErbB2-overexpressing breast cancer cells. Cancer Res 2002; 62(20):5703–5710.PubMedGoogle Scholar
  50. 50.
    Zhang L, Lau YK, Xia W et al. Tyrosine kinase inhibitor emodin suppresses growth of HER-2/neu-overexpressing breast cancer cells in athymic mice and sensitizes these cells to the inhibitory effect of paclitaxel. Clin Cancer Res 1999; 5:343–353.PubMedGoogle Scholar
  51. 51.
    Ueno NT, Yu D, Hung MC. Chemosensitization of HER-2/neu-overexpressing human breast cancer cells to paclitaxol (Taxol) by adenovirus type 5 E1A. Oncogene 1997; 15:953–960.CrossRefPubMedGoogle Scholar
  52. 52.
    Ueno NT, Bartholomeusz C, Xia W et al. Systemic gene therapy in human xenograft tumor models by liposomal delivery of the E1A gene. Cancer Res 2002; 62(22):6712–6716.PubMedGoogle Scholar
  53. 53.
    Sjostrom J, Collan J, von Boguslawski K et al. C-erbB-2 expression does not predict response to docetaxel or sequential methotrexate and 5-fluorouracil in advanced breast cancer. Eur J Cancer 2002; 38(4):535–542.CrossRefPubMedGoogle Scholar
  54. 54.
    Rozan S, Vincent-Salomon A, Zafrani B et al. No significant predictive value of c-erbB-2 or p53 expression regarding sensitivity to primary chemotherapy or radiotherapy in breast cancer. Int J Cancer 1998; 79:27–33.CrossRefPubMedGoogle Scholar
  55. 55.
    Porter-Jordan K, Lippman ME. Overview of the biologic markers of breast cancer. Breast Cancer 1994; 8:73–100.Google Scholar
  56. 56.
    Ross JS, Fletcher JA, Bloom KJ et al. HER-2/neu testing in breast cancer. Am J Clin Pathol 2003; 120(Suppl):S53–71.Google Scholar
  57. 57.
    Yu D, Hung M-C. Role of erbB2 in breast cancer chemosensitivity. BioEssays 2000; 22:673–680.CrossRefPubMedGoogle Scholar
  58. 58.
    Pegram MD, Finn RS, Arzoo K et al. The effect of HER2/neu overexpression on chemotherapeutic drug sensitivity in human breast and ovarian cancer cells. Oncogene 1997; 15:537–547.CrossRefPubMedGoogle Scholar
  59. 59.
    Pietras RJ, Pegram MD, Finn RS et al. Remission of human breast cancer xenografts on therapy with humanized monoclonal antibody to HER-2 receptor and DNA-reactive drugs. Oncogene 1998; 17:2235–2249.CrossRefPubMedGoogle Scholar
  60. 60.
    Alaoui-Jamali MA, Paterson J, Al Moustafa AE et al. The role of erbB-2 tyrosine kinase receptor in cellular intrinsic chemoresistance: Mechanisms and implications. Biochem Cell Biol 1997; 75:315–325.CrossRefPubMedGoogle Scholar
  61. 61.
    Fisher DE. Apoptosis in cancer therapy: Crossing the threshold. Cell 1994; 78:539–542.CrossRefPubMedGoogle Scholar
  62. 62.
    Wang CY, Cusack Jr JC, Liu R et al. Control of inducible chemoresistance: Enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB. Nat Med 1999; 5(4):412–417.CrossRefPubMedGoogle Scholar
  63. 63.
    Gao CY, Zelenka PS. Induction of cyclin B and H1 kinase activity in apoptotic PC12 cells. Exp Cell Res 1995; 219:612–618.CrossRefPubMedGoogle Scholar
  64. 64.
    Yu D, Jing T, Liu B et al. Overexpression of ErbB2 blocks Taxol-induced apoptosis by upregulation of p21Cip1, which inhibits p34Cdc2 kinase. Mol Cell 1998; 2(5):581–591.CrossRefPubMedGoogle Scholar
  65. 65.
    Yang W, Klos KS, Zhou X et al. ErbB2 overexpression in human breast carcinoma is correlated with p21Cip1 up-regulation and tyrosine-15 hyperphosphorylation of p34Cdc2: Poor responsiveness to chemotherapy with cyclophoshamide methotrexate, and 5-fluorouracil is associated with Erb2 overexpression and with p21Cip1 overexpression. Cancer 2003; 98(6):1123–1130.CrossRefPubMedGoogle Scholar
  66. 66.
    Osborne CK, Bardou V, Hopp TA et al. Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer. J Natl Cancer Inst 2003; 95(5):353–361.PubMedGoogle Scholar
  67. 67.
    Shou J, Massarweh S, Osborne CK et al. Mechanisms of tamoxifen resistance: Increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. J Natl Cancer Inst 2004; 96(12):926–935.PubMedGoogle Scholar
  68. 68.
    Nagata Y, Lan KH, Zhou X et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 2004; 6(2):117–127.CrossRefPubMedGoogle Scholar
  69. 69.
    Le XF, Claret FX, Lammayot A et al. The role of cyclin-dependent kinase inhibitor p27Kip1 in anti-HER2 antibody-induced G1 cell cycle arrest and tumor growth inhibition. J Biol Chem 2003; 278(26):23441–23451.CrossRefPubMedGoogle Scholar
  70. 70.
    Nahta R, Takahashi T, Ueno NT et al. P27(kip1) down-regulation is associated with trastuzumab resistance in breast cancer cells. Cancer Res 2004; 64(11):3981–3986.CrossRefPubMedGoogle Scholar
  71. 71.
    Baselga J, Tripathy D, Mendelsohn J et al. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol 1996; 14(3):737–744.PubMedGoogle Scholar
  72. 72.
    Yu D, Scorsone K, Hung M-C. Adenovirus type 5 E1A gene products act as transformation suppressors of the neu oncogene. Mol Cell Biol 1991; 11(3):1745–1750.PubMedGoogle Scholar
  73. 73.
    Yu DH, Hamada JI, Zhang H et al. Mechanisms of c-erbB2/neu oncogene-induced metastasis and repression of metastatic properties by adenovirus 5 E1A gene products. Oncogene 1992; 7:2263–2270.PubMedGoogle Scholar
  74. 74.
    Yu D, Suen T-C, Yan D-H et al. Transcriptional repression of the neu protooncogene by the adenovirus 5 E1A gene products. Proc Natl Acad Sci USA 1990; 87(12):4499–4503.CrossRefPubMedGoogle Scholar
  75. 75.
    Yu D, Matin A, Xia W et al. Liposome-mediated in vivo E1A gene transfer suppressed dissemination of ovarian cancer cells that overexpress HER-2/neu. Oncogene 1995; 11:1383–1388.PubMedGoogle Scholar
  76. 76.
    Liao Y, Zou YY, Xia WY et al. Enhanced paclitaxel cytotoxicity and prolonged animal survival rate by a nonviral-mediated systematic delivery of E1A gene in orthotopic xenograft human breast cancer. Cancer Gene Ther 2004; 11(9):594–602.CrossRefPubMedGoogle Scholar
  77. 77.
    Spector NL, Xia W, Burris IIIrd H et al. Study of the biological effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosines kinases, on tumor growth and survival pathways in patients with advanced malignancies. J Clin Oncol 2005; (Epub ahead of print_.Google Scholar
  78. 78.
    Deshane J, Loechel F, Conry RM et al. Intracellular single-chain antibody directed against erbB2 down-regulates cell surface erbB2 and exhibits a selective anti-proliferative effect in erbB2 overexpressing cancer cell lines. Gene Ther 1994; 1(5):332–337.PubMedGoogle Scholar
  79. 79.
    Barnes MN, Deshane JS, Siegal GP et al. Novel gene therapy strategy to accomplish growth factor modulation induces enhanced tumor cell chemosensitivity. Clin Cancer Res 1996; 2:1089–1095.PubMedGoogle Scholar
  80. 80.
    Rait AS, Pirollo KF, Xiang L et al. Tumor-targeting, systemically delivered antisense HER-2 chemosensitizes human breast cancer xenografts irrespective of HER-2 levels. Mol Med 2002; 8(8):475–486.PubMedGoogle Scholar
  81. 81.
    Rait AS, Pirollo KF, Ulick D et al. HER-2-targeted antisense oligonucleotide results in sensitization of head and neck cancer cells to chemotherapeutic agents. Ann NY Acad Sci 2003; 1002:78–89.CrossRefPubMedGoogle Scholar
  82. 82.
    Waterhouse DN, Dragowska WH, Gelmon KA et al. Pharmacodynamic behavior of liposomal antisense oligonucleotides targeting Her-2/neu and vascular endothelial growth factor in an ascitic MDA435/LCC6 human breast cancer model. Cancer Biol Ther 2004; 3(2):197–204.PubMedGoogle Scholar
  83. 83.
    Funato T, Kozawa K, Fujimaki S et al. Increased sensitivity to cisplatin in gastric cancer by antisense inhibition of the her-2/neu (c-erbB-2) gene. Chemotherapy 2001; 47(4):297–303.CrossRefPubMedGoogle Scholar
  84. 84.
    Park BW, Berezov A, Wu CW et al. Rationally designed anti-HER2/neu peptide mimetic disables p185HER2/neu tyrosine kinases in vitro and in vivo. Nat Biotech 2000; 18:194–198.CrossRefGoogle Scholar
  85. 85.
    Berezov A, Chen J, Liu Q et al. Disabling receptor ensembles with rationally designed interface peptidomimetics. J Biol Chem 2002; 277(31):28330–28339.CrossRefPubMedGoogle Scholar
  86. 86.
    Murali R, Liu Q, Cheng X et al. Antibody like peptidomimetics as large scale immunodetection probes. Cell Mol Biol 2003; 49(2):209–216.PubMedGoogle Scholar
  87. 87.
    Grunt T, Dittrich E, Ofterdinger M et al. Effects of retinoic acid and fenretinide on the c-erbB-2 expression, growth and cisplatin sensitivity of breast cancer cells. Br J Cancer 1998; 78:79–87.PubMedGoogle Scholar
  88. 88.
    Mellinghoff IK, Vivanco I, Kwon A et al. HER2/neu kinase-dependent modulation of androgen receptor function through effects on DNA binding and stability. Cancer Cell 2004; 6(5):517–527.CrossRefPubMedGoogle Scholar
  89. 89.
    Yang G, Cai KQ, Thompson-Lanza JA et al. Inhibition of breast and ovarian tumor growth through multiple signaling pathways by using retrovirus-mediated small interfering RNA against Her-2/neu gene expression. J Biol Chem 2004; 279(6):4339–4345.CrossRefPubMedGoogle Scholar
  90. 90.
    Choudhury A, Chaoro J, Parapuram SK et al. Small interfering RNA (siRNA) inhibits the expression of the Her2/neu gene, upregulates HLA class I and induces apoptosis of Her2/neu positive tumor cell lines. Int J Cancer 2004; 108(1):71–77.CrossRefPubMedGoogle Scholar
  91. 91.
    Hayes DF, Henderson IC, Shapiro CL. Treatment of metastatic breast cancer: Present and future prospects. Seminars in Oncol 1995; 22(2):5–21.Google Scholar
  92. 92.
    Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 2003; 55(3):329–347.CrossRefPubMedGoogle Scholar
  93. 93.
    Brannon Peppa L, Blachette JO. Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev 2004; 56(11):1649–1659.CrossRefGoogle Scholar
  94. 94.
    Garber K. Improved Paclitaxel formulation hints at new chemotherapy approach. J Natl Cancer Inst 2004; 96(2):90–91.PubMedCrossRefGoogle Scholar
  95. 95.
    Ito A, Kuga Y, Honda H et al. Magnetite nanoparticle-loaded anti-HER2 immunoliposomes for combination of antibody therapy with hyperthermia. Cancer Lett 2004; 212(2):167–175.CrossRefPubMedGoogle Scholar

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© Landes Bioscience and Springer Science+Business Media 2007

Authors and Affiliations

  1. 1.Department of Surgical OncologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA

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