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Novel Signaling Pathways in Breast Cancer

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Breast Cancer and Molecular Medicine

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References

  1. Baselga, J., Norton, L. Focus on breast cancer. Cancer Cell 1, 319–22 (2002).

    Article  PubMed  CAS  Google Scholar 

  2. Zhou, B. P., Hung, M. C. Dysregulation of cellular signaling by HER2/neu in breast cancer. Semin Oncol 30, 38–48 (2003).

    Article  PubMed  CAS  Google Scholar 

  3. Wang, S. C., Zhang, L., Hortobagyi, G. N., Hung, M. C. Targeting HER2: recent developments and future directions for breast cancer patients. Semin Oncol 28, 21–9 (2001).

    Article  PubMed  Google Scholar 

  4. Craven, R. J., Lightfoot, H., Cance, W. G. A decade of tyrosine kinases: from gene discovery to therapeutics. Surg Oncol 12, 39–49 (2003).

    Article  PubMed  Google Scholar 

  5. Bacus, S. S., Chin, D., Yarden, Y., Zelnick, C. R., Stern, D. F. Type 1 receptor tyrosine kinases are differentially phosphorylated in mammary carcinoma and differentially associated with steroid receptors. Am J Pathol 148, 549–58 (1996).

    PubMed  CAS  Google Scholar 

  6. Cohen, S., Taylor, J. M. Epidermal growth factor: chemical and biological characterization. Recent Prog Horm Res 30, 533–50 (1974).

    PubMed  CAS  Google Scholar 

  7. Cohen, S., Fava, R. A., Sawyer, S. T. Purification and characterization of epidermal growth factor receptor/protein kinase from normal mouse liver. Proc Natl Acad Sci U S A 79, 6237–41 (1982).

    Article  PubMed  CAS  Google Scholar 

  8. Cohen, S., Ushiro, H., Stoscheck, C., Chinkers, M. A native 170,000 epidermal growth factor receptor-kinase complex from shed plasma membrane vesicles. J Biol Chem 257, 1523–31 (1982).

    PubMed  CAS  Google Scholar 

  9. Haigler, H. T., McKanna, J. A., Cohen, S. Direct visualization of the binding and internalization of a ferritin conjugate of epidermal growth factor in human carcinoma cells A-431. J Cell Biol 81, 382–95 (1979).

    Article  PubMed  CAS  Google Scholar 

  10. Carpenter, G. ErbB-4: mechanism of action and biology. Exp Cell Res 284, 66–77 (2003).

    Article  PubMed  CAS  Google Scholar 

  11. Anderson, D. et al. Binding of SH2 domains of phospholipase C gamma 1, GAP, and Src to activated growth factor receptors. Science 250, 979–82 (1990).

    Article  PubMed  CAS  Google Scholar 

  12. Navolanic, P. M., Steelman, L. S., McCubrey, J. A. EGFR family signaling and its association with breast cancer development and resistance to chemotherapy (Review). Int J Oncol 22, 237–52 (2003).

    PubMed  CAS  Google Scholar 

  13. Yang, Y. et al. Sequential requirement of hepatocyte growth factor and neuregulin in the morphogenesis and differentiation of the mammary gland. J Cell Biol 131, 215–26 (1995).

    Article  PubMed  CAS  Google Scholar 

  14. Sebastian, J. et al. Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis. Cell Growth Differ 9, 777–85 (1998).

    PubMed  CAS  Google Scholar 

  15. Schroeder, J. A., Lee, D. C. Dynamic expression and activation of ERBB receptors in the developing mouse mammary gland. Cell Growth Differ 9, 451–64 (1998).

    PubMed  CAS  Google Scholar 

  16. Xie, W., Paterson, A. J., Chin, E., Nabell, L. M., Kudlow, J. E. Targeted expression of a dominant negative epidermal growth factor receptor in the mammary gland of transgenic mice inhibits pubertal mammary duct development. Mol Endocrinol 11, 1766–81 (1997).

    Article  PubMed  CAS  Google Scholar 

  17. Lemoine, N. R. et al. Expression of the ERBB3 gene product in breast cancer. Br J Cancer 66, 1116–21 (1992).

    PubMed  CAS  Google Scholar 

  18. Travis, A. et al. C-erbB-3 in human breast carcinoma: expression and relation to prognosis and established prognostic indicators. Br J Cancer 74, 229–33 (1996).

    PubMed  CAS  Google Scholar 

  19. Bieche, I. et al. Prognostic value of ERBB family mRNA expression in breast carcinomas. Int J Cancer 106, 758–65 (2003).

    Article  PubMed  CAS  Google Scholar 

  20. Vogt, U. et al. Amplification of erbB-4 oncogene occurs less frequently than that of erbB-2 in primary human breast cancer. Gene 223, 375–80 (1998).

    Article  PubMed  CAS  Google Scholar 

  21. Kew, T. Y. et al. c-erbB-4 protein expression in human breast cancer. Br J Cancer 82, 1163–70 (2000).

    Article  PubMed  CAS  Google Scholar 

  22. Knowlden, J. M. et al. c-erbB3 and c-erbB4 expression is a feature of the endocrine responsive phenotype in clinical breast cancer. Oncogene 17, 1949–57 (1998).

    Article  PubMed  CAS  Google Scholar 

  23. Petrocelli, T., Slingerland, J. M. PTEN deficiency: a role in mammary carcinogenesis. Breast Cancer Res 3, 356–60 (2001).

    Article  PubMed  CAS  Google Scholar 

  24. Shi, W. et al. Dysregulated PTEN-PKB and negative receptor status in human breast cancer. Int J Cancer 104, 195–203 (2003).

    Article  PubMed  CAS  Google Scholar 

  25. Zhou, B. P. et al. Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells. Nat Cell Biol 3, 245–52 (2001).

    Article  PubMed  CAS  Google Scholar 

  26. Zhou, B. P. et al. HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nat Cell Biol 3, 973–82 (2001).

    Article  PubMed  CAS  Google Scholar 

  27. Li, Y., Dowbenko, D., Lasky, L. A. AKT/PKB phosphorylation of p21Cip/WAF1 enhances protein stability of p21Cip/WAF1 and promotes cell survival. J Biol Chem 277, 11352–61 (2002).

    Article  PubMed  CAS  Google Scholar 

  28. El-Deiry, W. S. Akt takes centre stage in cell-cycle deregulation. Nat Cell Biol 3, E71–3 (2001).

    Article  PubMed  CAS  Google Scholar 

  29. Rossig, L. et al. Akt-dependent phosphorylation of p21(Cip1) regulates PCNA binding and proliferation of endothelial cells. Mol Cell Biol 21, 5644–57 (2001).

    Article  PubMed  CAS  Google Scholar 

  30. Asada, M. et al. Apoptosis inhibitory activity of cytoplasmic p21(Cip1/WAF1) in monocytic differentiation. EMBO J 18, 1223–34 (1999).

    Article  PubMed  CAS  Google Scholar 

  31. Huang, S. et al. Sustained activation of the JNK cascade and rapamycin-induced apoptosis are suppressed by p53/p21(Cip1). Mol Cell 11, 1491–501 (2003).

    Article  PubMed  CAS  Google Scholar 

  32. Winters, Z. E. et al. Subcellular localisation of cyclin B, Cdc2 and p21(WAF1/CIP1) in breast cancer. association with prognosis. Eur J Cancer 37, 2405–12 (2001).

    Article  PubMed  CAS  Google Scholar 

  33. Xia, W. et al. Phosphorylation/cytoplasmic localization of p21 Cip1/WAF1 is associated with Her2/Neu overexpression and provides a novel combination predictor for worse prognosis in breast cancer patients. Clinical Cancer Research (2004).

    Google Scholar 

  34. Blain, S. W., Massague, J. Breast cancer banishes p27 from nucleus. Nat Med 8, 1076–8 (2002).

    Article  PubMed  CAS  Google Scholar 

  35. Liang, J. et al. PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest. Nat Med 8, 1153–60 (2002).

    Article  PubMed  CAS  Google Scholar 

  36. Shin, I. et al. PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization. Nat Med 8, 1145–52 (2002).

    Article  PubMed  CAS  Google Scholar 

  37. Viglietto, G. et al. Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer. Nat Med 8, 1136–44 (2002).

    Article  PubMed  CAS  Google Scholar 

  38. Clarke, R. B. p27KIP1 phosphorylation by PKB/Akt leads to poor breast cancer prognosis. Breast Cancer Res 5, 162–3 (2003).

    Article  PubMed  Google Scholar 

  39. Honda, R., Tanaka, H., Yasuda, H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett 420, 25–7 (1997).

    Article  PubMed  CAS  Google Scholar 

  40. Knuefermann, C. et al. HER2/PI-3K/Akt activation leads to a multidrug resistance in human breast adenocarcinoma cells. Oncogene 22, 3205–12 (2003).

    Article  PubMed  CAS  Google Scholar 

  41. Ogawara, Y. et al. Akt enhances Mdm2-mediated ubiquitination and degradation of p53. J Biol Chem 277, 21843–50 (2002).

    Article  PubMed  CAS  Google Scholar 

  42. Mayo, L. D., Donner, D. B. A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc Natl Acad Sci U S A 98, 11598–603 (2001).

    Article  PubMed  CAS  Google Scholar 

  43. Marti, U., Hug, M. Acinar and cellular distribution and mRNA expression of the epidermal growth factor receptor are changed during liver regeneration. J Hepatol 23, 318–27 (1995).

    PubMed  CAS  Google Scholar 

  44. Marti, U. et al. Localization of epidermal growth factor receptor in hepatocyte nuclei. Hepatology 13, 15–20 (1991).

    Article  PubMed  CAS  Google Scholar 

  45. Lin, S. Y. et al. Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat Cell Biol 3, 802–8 (2001).

    Article  PubMed  CAS  Google Scholar 

  46. Carpenter, G. Nuclear localization and possible functions of receptor tyrosine kinases. Curr Opin Cell Biol 15, 143–8 (2003).

    Article  PubMed  CAS  Google Scholar 

  47. Wells, A., Marti, U. Signalling shortcuts: cell-surface receptors in the nucleus? Nat Rev Mol Cell Biol 3, 697–702 (2002).

    Article  PubMed  CAS  Google Scholar 

  48. Xie, Y., Hung, M. C. Nuclear localization of p185neu tyrosine kinase and its association with transcriptional transactivation. Biochem Biophys Res Commun 203, 1589–98 (1994).

    Article  PubMed  CAS  Google Scholar 

  49. Offterdinger, M., Schofer, C., Weipoltshammer, K., Grunt, T. W. c-erbB-3: a nuclear protein in mammary epithelial cells. J Cell Biol 157, 929–39 (2002).

    Article  PubMed  CAS  Google Scholar 

  50. Ni, C. Y., Murphy, M. P., Golde, T. E., Carpenter, G. Gamma-secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science 294, 2179–81 (2001).

    Article  PubMed  CAS  Google Scholar 

  51. Zhang, F. X. et al. Neurotrophin receptor immunostaining in the vestibular nuclei of rats. Neuroreport 14, 851–5 (2003).

    Article  PubMed  CAS  Google Scholar 

  52. Rakowicz-Szulczynska, E. M., Herlyn, M., Koprowski, H. Nerve growth factor receptors in chromatin of melanoma cells, proliferating melanocytes, and colorectal carcinoma cells in vitro. Cancer Res 48, 7200–6 (1988).

    PubMed  CAS  Google Scholar 

  53. Zwaagstra, J. C., Guimond, A., O’Connor-McCourt, M. D. Predominant intracellular localization of the type I transforming growth factor-beta receptor and increased nuclear accumulation after growth arrest. Exp Cell Res 258, 121–34 (2000).

    Article  PubMed  CAS  Google Scholar 

  54. Maher, P. A. Nuclear Translocation of fibroblast growth factor (FGF) receptors in response to FGF-2. J Cell Biol 134, 529–36 (1996).

    Article  PubMed  CAS  Google Scholar 

  55. Reilly, J. F., Maher, P. A. Importin beta-mediated nuclear import of fibroblast growth factor receptor: role in cell proliferation. J Cell Biol 152, 1307–12 (2001).

    Article  PubMed  CAS  Google Scholar 

  56. Gohring, U. J. et al. Immunohistochemical detection of epidermal growth factor receptor lacks prognostic significance for breast carcinoma. J Soc Gynecol Investig 2, 653–9 (1995).

    Article  PubMed  CAS  Google Scholar 

  57. Kamio, T., Shigematsu, K., Sou, H., Kawai, K., Tsuchiyama, H. Immunohistochemical expression of epidermal growth factor receptors in human adrenocortical carcinoma. Hum Pathol 21, 277–82 (1990).

    Article  PubMed  CAS  Google Scholar 

  58. Lipponen, P., Eskelinen, M. Expression of epidermal growth factor receptor in bladder cancer as related to established prognostic factors, oncoprotein (c-erbB-2, p53) expression and long-term prognosis. Br J Cancer 69, 1120–5 (1994).

    PubMed  CAS  Google Scholar 

  59. Toft, D., Gorski, J. A receptor molecule for estrogens: isolation from the rat uterus and preliminary characterization. Proc Natl Acad Sci U S A 55, 1574–81 (1966).

    Article  PubMed  CAS  Google Scholar 

  60. Kuiper, G. G., Enmark, E., Pelto-Huikko, M., Nilsson, S., Gustafsson, J. A. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A 93, 5925–30 (1996).

    Article  PubMed  CAS  Google Scholar 

  61. Ali, S., Coombes, R. C. Endocrine-responsive breast cancer and strategies for combating resistance. Nat Rev Cancer 2, 101–12 (2002).

    Article  PubMed  Google Scholar 

  62. Kuukasjarvi, T., Kononen, J., Helin, H., Holli, K., Isola, J. Loss of estrogen receptor in recurrent breast cancer is associated with poor response to endocrine therapy. J Clin Oncol 14, 2584–9 (1996).

    PubMed  CAS  Google Scholar 

  63. Clarke, R. et al. Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling. Oncogene 22, 7316–39 (2003).

    Article  PubMed  CAS  Google Scholar 

  64. Moggs, J. G., Orphanides, G. Estrogen receptors: orchestrators of pleiotropic cellular responses. EMBO Rep 2, 775–81 (2001).

    Article  PubMed  CAS  Google Scholar 

  65. Strahl, B. D., Allis, C. D. The language of covalent histone modifications. Nature 403, 41–5 (2000).

    Article  PubMed  CAS  Google Scholar 

  66. Neuman, E. et al. Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4. Mol Cell Biol 17, 5338–47 (1997).

    PubMed  CAS  Google Scholar 

  67. Zwijsen, R. M. et al. CDK-independent activation of estrogen receptor by cyclin D1. Cell 88, 405–15 (1997).

    Article  PubMed  CAS  Google Scholar 

  68. Wang, T. C. et al. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature 369, 669–71 (1994).

    Article  PubMed  CAS  Google Scholar 

  69. Simoncini, T. et al. Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature 407, 538–41 (2000).

    Article  PubMed  CAS  Google Scholar 

  70. Campbell, R. A. et al. Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance. J Biol Chem 276, 9817–24 (2001).

    Article  PubMed  CAS  Google Scholar 

  71. Kousteni, S. et al. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell 104, 719–30 (2001).

    PubMed  CAS  Google Scholar 

  72. Martin, M. B., Stoica, A. Insulin-like growth factor-I and estrogen interactions in breast cancer. J Nutr 132, 3799S–3801S (2002).

    PubMed  Google Scholar 

  73. Hamelers, I. H., Steenbergh, P. H. Interactions between estrogen and insulin-like growth factor signaling pathways in human breast tumor cells. Endocr Relat Cancer 10, 331–45 (2003).

    Article  PubMed  CAS  Google Scholar 

  74. Sun, M. et al. Phosphatidylinositol-3-OH Kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K. Cancer Res 61, 5985–91 (2001).

    PubMed  CAS  Google Scholar 

  75. Castoria, G. et al. PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells. EMBO J 20, 6050–9 (2001).

    Article  PubMed  CAS  Google Scholar 

  76. Kato, S. et al. Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science 270, 1491–4 (1995).

    Article  PubMed  CAS  Google Scholar 

  77. Gee, J. M., Robertson, J. F., Ellis, I. O., Nicholson, R. I. Phosphorylation of ERK1/2 mitogen-activated protein kinase is associated with poor response to anti-hormonal therapy and decreased patient survival in clinical breast cancer. Int J Cancer 95, 247–54 (2001).

    Article  PubMed  CAS  Google Scholar 

  78. Nicholson, R. I. et al. Modulation of epidermal growth factor receptor in endocrine-resistant, oestrogen receptor-positive breast cancer. Endocr Relat Cancer 8, 175–82 (2001).

    Article  PubMed  CAS  Google Scholar 

  79. Lee, A. V., Weng, C. N., Jackson, J. G., Yee, D. Activation of estrogen receptor-mediated gene transcription by IGF-I in human breast cancer cells. J Endocrinol 152, 39–47 (1997).

    Article  PubMed  CAS  Google Scholar 

  80. Kahlert, S. et al. Estrogen receptor alpha rapidly activates the IGF-1 receptor pathway. J Biol Chem 275, 18447–53 (2000).

    Article  PubMed  CAS  Google Scholar 

  81. Kumar, R. Another tie that binds the MTA family to breast cancer. Cell 113, 142–3 (2003).

    Article  PubMed  CAS  Google Scholar 

  82. Lapidus, R. G., Nass, S. J., Davidson, N. E. The loss of estrogen and progesterone receptor gene expression in human breast cancer. J Mammary Gland Biol Neoplasia 3, 85–94 (1998).

    Article  PubMed  CAS  Google Scholar 

  83. Fujita, N. et al. MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer. Cell 113, 207–19 (2003).

    Article  PubMed  CAS  Google Scholar 

  84. Goodsell, D. S. The molecular perspective: cadherin. Oncologist 7, 467–8 (2002).

    Article  PubMed  CAS  Google Scholar 

  85. Okegawa, T., Li, Y., Pong, R. C., Hsieh, J. T. Cell adhesion proteins as tumor suppressors. J Urol 167, 1836–43 (2002).

    Article  PubMed  CAS  Google Scholar 

  86. Imhof, B. A., Vollmers, H. P., Goodman, S. L., Birchmeier, W. Cell-cell interaction and polarity of epithelial cells: specific perturbation using a monoclonal antibody. Cell 35, 667–75 (1983).

    Article  PubMed  CAS  Google Scholar 

  87. Behrens, J., Mareel, M. M., Van Roy, F. M., Birchmeier, W. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J Cell Biol 108, 2435–47 (1989).

    Article  PubMed  CAS  Google Scholar 

  88. Thiery, J. P. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2, 442–54 (2002).

    Article  PubMed  CAS  Google Scholar 

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Lo, HW., Wang, SC., Hung, MC. (2006). Novel Signaling Pathways in Breast Cancer. In: Piccart, M.J., Hung, MC., Solin, L.J., Cardoso, F., Wood, W.C. (eds) Breast Cancer and Molecular Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-28266-2_38

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