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08-SEPTEMBER-2008 09:13:22 - HER2/neu V-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog avian PDB rendering based on 1n8z. Available structures: 1n8z, 1s78, 2a91 Identifiers Symbols ERBB2; HER-2; HER-2/neu; HER2; NEU; NGL; TKR1; c-erb B2 External IDs OMIM: 164870 MGI: 95410 HomoloGene: 3273 Gene ontology Molecular function: nucleotide binding protein-tyrosine kinase activity non-membrane spanning protein tyrosine kinase activity receptor signaling protein tyrosine kinase activity receptor activity epidermal growth factor receptor activity iron ion binding ATP binding electron carrier activity transferase activity identical protein binding ErbB-3 class receptor binding protein heterodimerization activity Cellular component: extracellular region cytoplasm plasma membrane membrane integral to membrane apical plasma membrane Biological process: electron transport protein amino acid phosphorylation transmembrane receptor protein tyrosine kinase signaling pathway peripheral nervous system development heart development cell proliferation mammary gland development myelination positive regulation of MAPK activity regulation of angiogenesis phosphoinositide-mediated signaling positive regulation of epithelial cell proliferation RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 2064 13866 Ensembl ENSG00000141736 ENSMUSG00000062312 Uniprot P04626 Q80Y89 Refseq NM_001005862 mRNA NP_001005862 protein NM_001003817 mRNA NP_001003817 protein Location Chr 17: 35.1 - 35.14 Mb Chr 11: 98.23 - 98.25 Mb Pubmed search 1 2 HER2/neu also known as ErbB-2, ERBB2 stands for Human Epidermal growth factor Receptor 2 and is a protein giving higher aggressiveness in breast cancers. It is a member of the ErbB protein family, more commonly known as the epidermal growth factor receptor family. HER2/neu has also been designated as CD340 cluster of differentiation 340. Contents 1 Function 2 HER2 and cancer 3 Drugs targeting HER2 4 References 5 Further reading 6 External links Function HER2/neu is notable for its role in the pathogenesis of breast cancer and as a target of treatment. It is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation. HER2 is thought to be an orphan receptor, with none of the EGF family of ligands able to activate it. However, ErbB receptors dimerise on ligand binding, and HER2 is the preferential dimerisation partner of other members of the ErbB family.1 The HER2 gene is a proto-oncogene located at the long arm of human chromosome 1717q11.2-q12. HER2 and cancer Approximately 15-20 percent of breast cancers have an amplification of the HER2/neu gene or overexpression of its protein product.2 Overexpression of this receptor in breast cancer is associated with increased disease recurrence and worse prognosis. Because of its prognostic role as well as its ability to predict response to trastuzumab see below, breast tumors are routinely checked for overexpression of HER2/neu. Overexpression also occurs in other cancer such as ovarian cancer and stomach cancer. The oncogene neu is so-named because it was derived from a neuroglioblastoma cell line in rat. HER2 is named because it has similar structure to human epidermal growth factor receptor, or HER1. ErbB2 was named for its similarity to ErbB avian erythroblastosis oncogene B, the oncogene later found to code for EGFR. Gene cloning showed that neu, HER2, and ErbB2 were the same. HER2 is co-localized, and thus most of the time co-amplified with the gene GRB7, which is as well a proto-oncogene active in e.g. breast cancer, testicular germ cell tumor, gastric cancer, and esophageal cancer. Drugs targeting HER2 Clinically, HER2/neu is important as the target of the monoclonal antibody trastuzumab marketed as Herceptin. Trastuzumab is only effective in breast cancer where the HER2/neu receptor is overexpressed. One of the mechanisms of how traztuzumab works after it binds to HER2 is by increasing p27, a protein that halts cell proliferation 3. The HER2 gene overexpression can be suppressed by the amplification of other genes and the use of the drug Herceptin. Research is currently being conducted to discover which disregulated genes may have this desired effect. Another monoclonal antibody, Pertuzumab 3, which inhibits dimerization of HER2 and HER3 receptors, is in advanced clinical trials. References ^ Olayioye MA 2001. Update on HER-2 as a target for cancer therapy: intracellular signaling pathways of ErbB2/HER-2 and family members. Breast Cancer Res 3 6: 385-389. doi:10.1186/bcr327. PMID 11737890. ^ Entrez Gene: ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog avian. ^ XF Le, Franz Pruefer, Robert Bast. 2005. HER2-targeting antibodies modulate the cyclin-dependent kinase inhibitor p27Kip1 via multiple signaling pathways.. Cell Cycle 4 1: 87-95. PMID 15611642. Further reading Ross JS, Fletcher JA, Linette GP, et al. 2003. The Her-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy.. Oncologist 8 4: 307-25. PMID 12897328. Zhou BP, Hung MC 2003. Dysregulation of cellular signaling by HER2/neu in breast cancer.. Semin. Oncol. 30 5 Suppl 16: 38-48. PMID 14613025. Ménard S, Casalini P, Campiglio M, et al. 2005. Role of HER2/neu in tumor progression and therapy.. Cell. Mol. Life Sci. 61 23: 2965-78. doi:10.1007/s00018-004-4277-7. PMID 15583858. Becker JC, Muller-Tidow C, Serve H, et al. 2006. Role of receptor tyrosine kinases in gastric cancer: new targets for a selective therapy.. World J. Gastroenterol. 12 21: 3297-305. PMID 16733844. Laudadio J, Quigley DI, Tubbs R, Wolff DJ 2007. HER2 testing: a review of detection methodologies and their clinical performance.. Expert Rev. Mol. Diagn. 7 1: 53-64. doi:10.1586/14737159.7.1.53. PMID 17187484. Bianchi F, Tagliabue E, Ménard S, Campiglio M 2007. Fhit expression protects against HER2-driven breast tumor development: unraveling the molecular interconnections.. Cell Cycle 6 6: 643-6. PMID 17374991. External links AACR Cancer Concepts Factsheet on HER2 Her2/neu Vaccine Protects Against Tumor Growth Chimeric molecules and Methods of Use MeSH Receptor,+erbB-2 This genetics article is a stub. v d e Proteins: clusters of differentiation see also list of human clusters of differentiation 1-50 CD1 a-c, 1A, 1D, 1E - CD2 - CD3 γ, δ, ε - CD4 - CD5 - CD6 - CD7 - CD8 a - CD9 - CD10 - CD11 a, b, c - CD13 - CD14 - CD15 - CD16 A, B - CD18 - CD19 - CD20 - CD21 - CD22 - CD23 - CD24 - CD25 - CD26 - CD27 - CD28 - CD29 - CD30 - CD31 - CD32 A, B - CD33 - CD34 - CD35 - CD36 - CD37 - CD38 - CD39 - CD40 - CD41- CD42 a, b, c, d - CD43 - CD44 - CD45 - CD46 - CD47 - CD48 - CD49 a, b, c, d, e, f - CD50 51-100 CD51 - CD52 - CD53 - CD54 - CD55 - CD56 - CD57- CD58 - CD59 - CD61 - CD62 E, L, P - CD63 - CD64 - CD66 a, b, c, d, e, f - CD68 - CD69 - CD70 - CD71 - CD72 - CD73 - CD74 - CD79 a, b - CD80 - CD81 - CD82 - CD83 - CD84 - CD85 a, d, e, h, j, k - CD86 - CD87 - CD88 - CD89 - CD90 - CD91- CD92 - CD93 - CD94 - CD95 - CD97 - CD98 - CD99 - CD100 101-150 CD101 - CD102 - CD103 - CD104 - CD105 - CD106 - CD107 a, b - CD108 - CD109 - CD110 - CD111 - CD112 - CD113 - CD114 - CD115 - CD116 - CD117 - CD118 - CD119 - CD120 a, b - CD121 a, b - CD122 - CD123 - CD124 - CD125 - CD126 - CD127 - CD129 - CD130 - CD131 - CD132 - CD133 - CD134 - CD135 - CD136 - CD137 - CD138 - CD140b - CD141 - CD142 - CD143 - CD144 - CD146 - CD147 - CD148 - CD150 151-200 CD151 - CD152 - CD153 - CD154 - CD155 - CD156 a, b, c - CD157 - CD158 a, d, e, i, k - CD159 a, c - CD160 - CD161 - CD162 - CD163 - CD164 - CD166 - CD167 a, b - CD168 - CD169 - CD170 - CD171 - CD172 a, b, g - CD174 - CD177 - CD178 - CD179 a, b - CD181 - CD182 - CD183 - CD184 - CD185 - CD186 - CD191 - CD192 - CD193 - CD194 - CD195 - CD196 - CD197 - CDw198 - CDw199 - CD200 201-250 CD201 - CD202b - CD204 - CD205 - CD206 - CD207 - CD208 - CD209 - CDw210 a, b - CD212 - CD213a 1, 2 - CD217 - CD218 a, b - CD220 - CD221 - CD222 - CD223 - CD224 - CD225 - CD226 - CD227 - CD228 - CD229 - CD230 - CD233 - CD234 - CD235 a, b - CD236 - CD238 - CD239 - CD240CE - CD241 - CD243 - CD244 - CD246 - CD247- CD248 - CD249 251-300 CD252 - CD253 - CD254 - CD256 - CD257 - CD258 - CD261 - CD262 - CD264 - CD265 - CD266 - CD267 - CD268 - CD269 - CD271 - CD272 - CD273 - CD274 - CD275 - CD276 - CD278 - CD279 - CD280 - CD281 - CD282 - CD283 - CD284 - CD286 - CD288 - CD289 - CD290 - CD292 - CDw293 - CD294 - CD295 - CD297 - CD298 - CD299 301-350 CD300A - CD304 - CD305 - CD307 - CD309 - CD312 - CD314 - CD315 - CD316 - CD317 - CD318 - CD320 - CD321 - CD322 - CD324 - CD325 - CD326 - CD328 - CD329 - CD331 - CD332 - CD333 - CD334 - CD335 - CD336 - CD337 - CD338 - CD339 - CD340 - CD344 - CD349 - CD350 v d e Oncogenes/Proto-oncogenes Extracellular/ Growth factor c-Sis Cell membrane/ receptor/tyrosine kinases c-ErbB HER2/neu, Her 3 - c-Kit - c-Met - c-Ret - Flt3 Cytoplasm c-Src Signal transduction/Serine/threonine-specific protein kinase: c-Raf - c-Ras HRAS - c-Akt Nucleus/Transcription factors AP-1 c-Fos, c-Jun - c-Myc - c-Mdm2 Other/ungrouped c-Bcl-2 - Notch - Stathmin v d e Transmembrane receptor, tyrosine kinase: receptor tyrosine kinases EC 2.7.10.1 I EGF HER2/neu, Her 3, Her 4 II Insulin - IGF-1 III Platelet-derived growth factor IV Fibroblast growth factor FGFR1, FGFR2, FGFR3 V VEGF receptors - Flk-1 - Flt-1 VII TRK: TrkA - TrkB - TrkC other VIII: Eph B2 - XI: Angiopoietin Receptors: Tie-1 Tie-2 - XIV: RET - XVI: Related to receptor tyrosine kinase - XVII: MuSK v d e Tumor markers Reproductive ovarian cancer: CA-125 - CD30 testicular cancer: βHCG - Alpha-fetoprotein/AFP-L3 - CD30 prostate cancer: Prostatic acid phosphatase - Prostate specific antigen - Glutamate carboxypeptidase II - erbB-3 receptor - Early prostate cancer antigen-2 - SPINK1 - GOLPH2 - PCA3 germ cell tumor: NANOG Digestive colorectal cancer: CA 19-9 hepatocellular carcinoma: Alpha-fetoprotein/AFP-L3 pancreatic cancer: CA 19-9 - Carcinoembryonic antigen Endocrine medullary thyroid cancer: Calcitonin pheochromocytoma: Normetanephrine - Enolase 2 Other breast cancer: CA 15-3 - erbB-2 receptor - erbB-3 receptor lung cancer: Carcinoembryonic antigen - Enolase 2 - Autocrine motility factor neuroendocrine tumors: Synaptophysin brain tumor: PCNA lymphoma: Neprilysin bladder cancer: erbB-3 receptor note: all are peptide except normetanephrine Retrieved from http://en..org/wiki/HER2/neu Categories: Genes on chromosome 17 | Human proteins | Genetics stubs | Cell signaling | Signal transduction | Clusters of differentiation | Tyrosine kinase receptors Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch Français 日本語 Tiếng Việt This page was last modified on 16 August 2008, at 19:26
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