HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Reese, D. M. Articles by Slamon, D. J. Search for Related Content PubMed PubMed Citation Articles by Reese, D. M. Articles by Slamon, D. J.

HER-2/neu Signal Transduction in Human Breast and Ovarian Cancer

Division of Hematology/Oncology and Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California, USA

Key Words. HER-2/neu • erbB receptors • Signal transduction • Breast cancer • Ovarian cancer • Heregulin • Epidermal growth factor

Correspondence: Dr. Dennis J. Slamon, University of California at Los Angeles, Department of Medicine, Division of Hematology/Oncology, 11-934 Factor Building, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.

The HER-2/neu proto-oncogene encodes a 185 kDa transmembrane receptor tyrosine kinase with significant sequence homology to other members of the class I receptor tyrosine kinase family. The HER-2/neu gene is amplified and/or overexpressed in 25%-30% of human breast and ovarian cancers, and overexpression of the receptor is associated with poor prognosis. Tyrosine phosphorylation and activation of the HER-2 receptor lead to activation of specific signal transduction pathways in breast and ovarian cancer cells, including the ras/MAP kinase cascade, phosphatidylinositol 3-kinase, and phospholipase C-. HER-2/neu signal transduction pathways ultimately converge on the cell nucleus, where the expression of diverse genes is induced after activation of the receptor. A more complete understanding of HER-2/neu signal transduction pathways may allow the development of specific therapeutics for the treatment of those human breast and ovarian cancers containing this alteration.

This article has been cited by other articles:

				J.-A Kim, Y.-J. Kang, G. Park, M. Kim, Y.-O. Park, H. Kim, S.-H. Leem, I.-S. Chu, J.-S. Lee, E.-H. Jho, et al. Identification of a Stroma-Mediated Wnt/{beta}-Catenin Signal Promoting Self-Renewal of Hematopoietic Stem Cells in the Stem Cell Niche Stem Cells, June 1, 2009; 27(6): 1318 - 1329. [Abstract] [Full Text] [PDF]

				L. M. McGlynn, T. Kirkegaard, J. Edwards, S. Tovey, D. Cameron, C. Twelves, J. M.S. Bartlett, and T. G. Cooke Ras/Raf-1/MAPK Pathway Mediates Response to Tamoxifen but not Chemotherapy in Breast Cancer Patients Clin. Cancer Res., February 15, 2009; 15(4): 1487 - 1495. [Abstract] [Full Text] [PDF]

				J. A. Fromm, S. A. S. Johnson, and D. L. Johnson Epidermal Growth Factor Receptor 1 (EGFR1) and Its Variant EGFRvIII Regulate TATA-Binding Protein Expression through Distinct Pathways Mol. Cell. Biol., October 15, 2008; 28(20): 6483 - 6495. [Abstract] [Full Text] [PDF]

				A. Scardino, M. Alimandi, P. Correale, S. G. Smith, R. Bei, H. Firat, M. G. Cusi, O. Faure, S. Graf-Dubois, G. Cencioni, et al. A Polyepitope DNA Vaccine Targeted to Her-2/ErbB-2 Elicits a Broad Range of Human and Murine CTL Effectors to Protect against Tumor Challenge Cancer Res., July 15, 2007; 67(14): 7028 - 7036. [Abstract] [Full Text] [PDF]

				Y.-J. Kang, S.-J. Yang, G. Park, B. Cho, C.-K. Min, T.-Y. Kim, J.-S. Lee, and I.-H. Oh A Novel Function of Interleukin-10 Promoting Self-Renewal of Hematopoietic Stem Cells Stem Cells, July 1, 2007; 25(7): 1814 - 1822. [Abstract] [Full Text] [PDF]

				S. Pervin, R. Singh, E. Hernandez, G. Wu, and G. Chaudhuri Nitric Oxide in Physiologic Concentrations Targets the Translational Machinery to Increase the Proliferation of Human Breast Cancer Cells: Involvement of Mammalian Target of Rapamycin/eIF4E Pathway Cancer Res., January 1, 2007; 67(1): 289 - 299. [Abstract] [Full Text] [PDF]

				Y.-J. Chung, B.-B. Park, Y.-J. Kang, T.-m. Kim, C. J. Eaves, and I.-H. Oh Unique effects of Stat3 on the early phase of hematopoietic stem cell regeneration Blood, August 15, 2006; 108(4): 1208 - 1215. [Abstract] [Full Text] [PDF]

				J. Wei, Y. Liu, S. Yang, J. Xu, H. Kong, B. Han, Y. Bao, Y. Wu, W. Yin, W. Li, et al. Screening of Single-Chain Variable Fragments against TSP50 from a Phage Display Antibody Library and Their Expression as Soluble Proteins J Biomol Screen, August 1, 2006; 11(5): 546 - 552. [Abstract] [PDF]

				S. D. Nathanson, R. Slater, D. DeBruyn, A. Kapke, and M. Linden HER-2/neu Expression in Primary Breast Cancer With Sentinel Lymph Node Metastasis Ann. Surg. Oncol., February 1, 2006; 13(2): 205 - 213. [Abstract] [Full Text] [PDF]

				N. Kroger, K. Milde-Langosch, S. Riethdorf, C. Schmoor, M. Schumacher, A. R. Zander, and T. Loning Prognostic and Predictive Effects of Immunohistochemical Factors in High-Risk Primary Breast Cancer Patients Clin. Cancer Res., January 1, 2006; 12(1): 159 - 168. [Abstract] [Full Text] [PDF]

				H. Okano, H. Shinohara, A. Miyamoto, K. Takaori, and N. Tanigawa Concomitant Overexpression of Cyclooxygenase-2 in HER-2-Positive on Smad4-Reduced Human Gastric Carcinomas Is Associated with a Poor Patient Outcome Clin. Cancer Res., October 15, 2004; 10(20): 6938 - 6945. [Abstract] [Full Text] [PDF]

				T. P. Kenny, C. L. Keen, P. Jones, H.-J. Kung, H. H. Schmitz, and M. E. Gershwin Cocoa Procyanidins Inhibit Proliferation and Angiogenic Signals in Human Dermal Microvascular Endothelial Cells Following Stimulation by Low-Level H2O2 Experimental Biology and Medicine, September 1, 2004; 229(8): 765 - 771. [Abstract] [Full Text] [PDF]

				S. K. Rabindran, C. M. Discafani, E. C. Rosfjord, M. Baxter, M. B. Floyd, J. Golas, W. A. Hallett, B. D. Johnson, R. Nilakantan, E. Overbeek, et al. Antitumor Activity of HKI-272, an Orally Active, Irreversible Inhibitor of the HER-2 Tyrosine Kinase Cancer Res., June 1, 2004; 64(11): 3958 - 3965. [Abstract] [Full Text] [PDF]

				A. F. Flint, L. U'Ren, M. E. Legare, S. J. Withrow, W. Dernell, and W. H. Hanneman Overexpression of the erbB-2 Proto-oncogene in Canine Osteosarcoma Cell Lines and Tumors Vet. Pathol., May 1, 2004; 41(3): 291 - 296. [Abstract] [Full Text] [PDF]

				I. B. Schiffer, S. Gebhard, C. K. Heimerdinger, A. Heling, J. Hast, U. Wollscheid, B. Seliger, B. Tanner, S. Gilbert, T. Beckers, et al. Switching Off HER-2/neu in a Tetracycline-Controlled Mouse Tumor Model Leads to Apoptosis and Tumor-Size-Dependent Remission Cancer Res., November 1, 2003; 63(21): 7221 - 7231. [Abstract] [Full Text] [PDF]

				M. L. Disis, N. Scholler, A. Dahlin, J. Pullman, K. L. Knutson, K.-E. Hellstrom, and I. Hellstrom Plasmid-based vaccines encoding rat neu and immune stimulatory molecules can elicit rat neu-specific immunity Mol. Cancer Ther., October 1, 2003; 2(10): 995 - 1002. [Abstract] [Full Text]

				V. P. Ramsauer, C. A. C. Carraway, P. J. I. Salas, and K. L. Carraway Muc4/Sialomucin Complex, the Intramembrane ErbB2 Ligand, Translocates ErbB2 to the Apical Surface in Polarized Epithelial Cells J. Biol. Chem., August 8, 2003; 278(32): 30142 - 30147. [Abstract] [Full Text] [PDF]

				J. Walker-Daniels, D. J. Riese II, and M. S. Kinch c-Cbl-Dependent EphA2 Protein Degradation Is Induced by Ligand Binding Mol. Cancer Res., November 1, 2002; 1(1): 79 - 87. [Abstract] [Full Text] [PDF]

				A. H. Talukder, R. Bagheri-Yarmand, R. R. E. Williams, J. Ragoussis, R. Kumar, and A. Raz Antihuman Epidermal Growth Factor Receptor 2 Antibody Herceptin Inhibits Autocrine Motility Factor (AMF) Expression and Potentiates Antitumor Effects of AMF Inhibitors Clin. Cancer Res., October 1, 2002; 8(10): 3285 - 3289. [Abstract] [Full Text] [PDF]

				A. Berezov, J. Chen, Q. Liu, H.-T. Zhang, M. I. Greene, and R. Murali Disabling Receptor Ensembles with Rationally Designed Interface Peptidomimetics J. Biol. Chem., July 26, 2002; 277(31): 28330 - 28339. [Abstract] [Full Text] [PDF]

				A. Scardino, D.-A. Gross, P. Alves, J. L. Schultze, S. Graff-Dubois, O. Faure, S. Tourdot, S. Chouaib, L. M. Nadler, F. A. Lemonnier, et al. HER-2/neu and hTERT Cryptic Epitopes as Novel Targets for Broad Spectrum Tumor Immunotherapy J. Immunol., June 1, 2002; 168(11): 5900 - 5906. [Abstract] [Full Text] [PDF]

				K. Subbaramaiah, L. Norton, W. Gerald, and A. J. Dannenberg Cyclooxygenase-2 Is Overexpressed in HER-2/neu-positive Breast Cancer. EVIDENCE FOR INVOLVEMENT OF AP-1 AND PEA3 J. Biol. Chem., May 17, 2002; 277(21): 18649 - 18657. [Abstract] [Full Text] [PDF]

				M. Hensel, A. Schneeweiss, H.-P. Sinn, G. Egerer, M. Kornacker, E. Solomayer, R. Haas, G. Bastert, and A. D. Ho Stem Cell Dose and Tumorbiologic Parameters as Prognostic Markers for Patients with Metastatic Breast Cancer Undergoing High-Dose Chemotherapy with Autologous Blood Stem Cell Support Stem Cells, January 1, 2002; 20(1): 32 - 40. [Abstract] [Full Text] [PDF]

				J. G. Christensen, R. E. Schreck, E. Chan, X. Wang, C. Yang, L. Liu, J. Cui, L. Sun, J. Wei, J. M. Cherrington, et al. High Levels of HER-2 Expression Alter the Ability of Epidermal Growth Factor Receptor (EGFR) Family Tyrosine Kinase Inhibitors to Inhibit EGFR Phosphorylation in Vivo Clin. Cancer Res., December 1, 2001; 7(12): 4230 - 4238. [Abstract] [Full Text] [PDF]

				I. Dybedal, D. Bryder, A. Fossum, L. S. Rusten, and S. E. W. Jacobsen Tumor necrosis factor (TNF)-mediated activation of the p55 TNF receptor negatively regulates maintenance of cycling reconstituting human hematopoietic stem cells Blood, September 15, 2001; 98(6): 1782 - 1791. [Abstract] [Full Text] [PDF]

				W. Feng, P. Webb, P. Nguyen, X. Liu, J. Li, M. Karin, and P. J. Kushner Potentiation of Estrogen Receptor Activation Function 1 (AF-1) by Src/JNK through a Serine 118-Independent Pathway Mol. Endocrinol., January 1, 2001; 15(1): 32 - 45. [Abstract] [Full Text]

				P. E. Blackshear Genetically Engineered Rodent Models of Mammary Gland Carcinogenesis: An Overview Toxicol Pathol, January 1, 2001; 29(1): 105 - 116. [Abstract] [PDF]

				M. Bissonnette, S. Khare, F. C. von Lintig, R. K. Wali, L. Nguyen, Y. Zhang, J. Hart, S. Skarosi, N. Varki, G. R. Boss, et al. Mutational and Nonmutational Activation of p21ras in Rat Colonic Azoxymethane-induced Tumors: Effects on Mitogen-activated Protein Kinase, Cyclooxygenase-2, and Cyclin D1 Cancer Res., August 1, 2000; 60(16): 4602 - 4609. [Abstract] [Full Text]

				X.-F. Le, R. Vadlamudi, A. McWatters, D. S. Bae, G. B. Mills, R. Kumar, and R. C. Bast Jr. Differential Signaling by an Anti-p185HER2 Antibody and Heregulin Cancer Res., July 1, 2000; 60(13): 3522 - 3531. [Abstract] [Full Text]

				Y. Nieto, P. J. Cagnoni, S. Nawaz, E. J. Shpall, R. Yerushalmi, B. Cook, P. Russell, J. McDermit, J. Murphy, S. I. Bearman, et al. Evaluation of the Predictive Value of Her-2/neu Overexpression and p53 Mutations in High-Risk Primary Breast Cancer Patients Treated With High-Dose Chemotherapy and Autologous Stem-Cell Transplantation J. Clin. Oncol., May 10, 2000; 18(10): 2070 - 2080. [Abstract] [Full Text] [PDF]

				S Wang, M H Saboorian, E Frenkel, L Hynan, S T Gokaslan, and R Ashfaq Laboratory assessment of the status of Her-2/neu protein and oncogene in breast cancer specimens: comparison of immunohistochemistry assay with fluorescence in situ hybridisation assays J. Clin. Pathol., May 1, 2000; 53(5): 374 - 381. [Abstract] [Full Text] [PDF]

				Z. Lu, A. Hornia, T. Joseph, T. Sukezane, P. Frankel, M. Zhong, S. Bychenok, L. Xu, L. A. Feig, and D. A. Foster Phospholipase D and RalA Cooperate with the Epidermal Growth Factor Receptor To Transform 3Y1 Rat Fibroblasts Mol. Cell. Biol., January 15, 2000; 20(2): 462 - 467. [Abstract] [Full Text]

				A. H. Talukder, R. Vadlamudi, M. Mandal, and R. Kumar Heregulin Induces Expression, DNA Binding Activity, and Transactivating Functions of Basic Leucine Zipper Activating Transcription Factor 4 Cancer Res., January 1, 2000; 60(2): 276 - 281. [Abstract] [Full Text]

				A. H. Talukder, L. Adam, A. Raz, and R. Kumar Heregulin Regulation of Autocrine Motility Factor Expression in Human Tumor Cells Cancer Res., January 1, 2000; 60(2): 474 - 480. [Abstract] [Full Text]

				X.-F. Le, A. McWatters, J. Wiener, J.-Y. Wu, G. B. Mills, and R. C. Bast Jr. Anti-HER2 Antibody and Heregulin Suppress Growth of HER2-Overexpressing Human Breast Cancer Cells through Different Mechanisms Clin. Cancer Res., January 1, 2000; 6(1): 260 - 270. [Abstract] [Full Text]

				J. Kassis, J. Moellinger, H. Lo, N. M. Greenberg, H.-G. Kim, and A. Wells A Role for Phospholipase C-{{gamma}}-mediated Signaling in Tumor Cell Invasion Clin. Cancer Res., August 1, 1999; 5(8): 2251 - 2260. [Abstract] [Full Text] [PDF]

				X. S. Wan, F. L. Meyskens Jr., W. B. Armstrong, T. H. Taylor, and A. R. Kennedy Relationship between Protease Activity and neu Oncogene Expression in Patients with Oral Leukoplakia Treated with the Bowman Birk Inhibitor Cancer Epidemiol. Biomarkers Prev., July 1, 1999; 8(7): 601 - 608. [Abstract] [Full Text]

				J. G. Hengstler, J. Lange, A. Kett, N. Dornhofer, R. Meinert, M. Arand, P. G. Knapstein, R. Becker, F. Oesch, and B. Tanner Contribution of c-erbB-2 and Topoisomerase II{{alpha}} to Chemoresistance in Ovarian Cancer Cancer Res., July 1, 1999; 59(13): 3206 - 3214. [Abstract] [Full Text] [PDF]

				R. Vadlamudi, L. Adam, B. Tseng, L. Costa, and R. Kumar Transcriptional Up-Regulation of Paxillin Expression by Heregulin in Human Breast Cancer Cells Cancer Res., June 1, 1999; 59(12): 2843 - 2846. [Abstract] [Full Text] [PDF]

				Z. Wang, L. Zhang, T. K. Yeung, and X. Chen Endocytosis Deficiency of Epidermal Growth Factor (EGF) Receptor-ErbB2 Heterodimers in Response to EGF Stimulation Mol. Biol. Cell, May 1, 1999; 10(5): 1621 - 1636. [Abstract] [Full Text]

				R. J. Pietras, J. C. Poen, D. Gallardo, P. N. Wongvipat, H. J. Lee, and D. J. Slamon Monoclonal Antibody to HER-2/neuReceptor Modulates Repair of Radiation-induced DNA Damage and Enhances Radiosensitivity of Human Breast Cancer Cells Overexpressing This Oncogene Cancer Res., March 1, 1999; 59(6): 1347 - 1355. [Abstract] [Full Text] [PDF]

				D. W. Fry, A. J. Bridges, W. A. Denny, A. Doherty, K. D. Greis, J. L. Hicks, K. E. Hook, P. R. Keller, W. R. Leopold, J. A. Loo, et al. Specific, irreversible inactivation of the epidermal growth factor receptor and erbB2, by a new class of tyrosine kinase inhibitor PNAS, September 29, 1998; 95(20): 12022 - 12027. [Abstract] [Full Text] [PDF]

				T. H. Brummendorf, W. Dragowska, J.M. J.M. Zijlmans, G. Thornbury, and P. M. Lansdorp Asymmetric Cell Divisions Sustain Long-Term Hematopoiesis from Single-sorted Human Fetal Liver Cells J. Exp. Med., September 21, 1998; 188(6): 1117 - 1124. [Abstract] [Full Text] [PDF]

				T. J. Preston, W. J. Muller, and G. Singh Scavenging of Extracellular H2O2 by Catalase Inhibits the Proliferation of HER-2/Neu-transformed Rat-1 Fibroblasts through the Induction of a Stress Response J. Biol. Chem., March 16, 2001; 276(12): 9558 - 9564. [Abstract] [Full Text] [PDF]