HER2/neu (also known as ErbB-2, gene|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 ErbBprotein family, more commonly known as the epidermal growth factor receptor family. HER2/neu has also been designated as CD340 ( cluster of differentiation340).
HER2/neu is notable for its role in the
pathogenesisof breast cancerand as a target of treatment. It is a cell membrane surface-bound receptor tyrosine kinaseand is normally involved in the signal transductionpathways 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.cite journal |author=Olayioye MA|title=Update on HER-2 as a target for cancer therapy: intracellular signaling pathways of ErbB2/HER-2 and family members|journal= Breast Cancer Res |volume= 3 |issue= 6 |pages= 385–389 |year= 2001|doi= 10.1186/bcr327 |pmid= 11737890] The "HER2" gene is a proto-oncogenelocated at the long arm of human chromosome 17(17q11.2-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. [cite web | title = Entrez Gene: ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2064| accessdate = ] 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 cancerand stomach cancer.
oncogene"neu" is so-named because it was derived from a neuroglioblastomacell 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.cite journal |author=XF Le, Franz Pruefer, Robert Bast.|title=HER2-targeting antibodies modulate the cyclin-dependent kinase inhibitor p27Kip1 via multiple signaling pathways.|journal= Cell Cycle |volume= 4 |issue= 1 |pages= 87–95 |year= 2005 |pmid= 15611642]
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 [http://www.healthvalue.net/EGFR-engl.html] , which inhibits dimerization of HER2 and HER3 receptors, is in advanced clinical trials.
*cite journal | author=Ross JS, Fletcher JA, Linette GP, "et al." |title=The Her-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. |journal=Oncologist |volume=8 |issue= 4 |pages= 307–25 |year= 2003 |pmid= 12897328 |doi=
*cite journal | author=Zhou BP, Hung MC |title=Dysregulation of cellular signaling by HER2/neu in breast cancer. |journal=Semin. Oncol. |volume=30 |issue= 5 Suppl 16 |pages= 38–48 |year= 2003 |pmid= 14613025 |doi=
*cite journal | author=Ménard S, Casalini P, Campiglio M, "et al." |title=Role of HER2/neu in tumor progression and therapy. |journal=Cell. Mol. Life Sci. |volume=61 |issue= 23 |pages= 2965–78 |year= 2005 |pmid= 15583858 |doi= 10.1007/s00018-004-4277-7
*cite journal | author=Becker JC, Muller-Tidow C, Serve H, "et al." |title=Role of receptor tyrosine kinases in gastric cancer: new targets for a selective therapy. |journal=World J. Gastroenterol. |volume=12 |issue= 21 |pages= 3297–305 |year= 2006 |pmid= 16733844 |doi=
*cite journal | author=Laudadio J, Quigley DI, Tubbs R, Wolff DJ |title=HER2 testing: a review of detection methodologies and their clinical performance. |journal=Expert Rev. Mol. Diagn. |volume=7 |issue= 1 |pages= 53–64 |year= 2007 |pmid= 17187484 |doi= 10.1586/1473718.104.22.168
*cite journal | author=Bianchi F, Tagliabue E, Ménard S, Campiglio M |title=Fhit expression protects against HER2-driven breast tumor development: unraveling the molecular interconnections. |journal=Cell Cycle |volume=6 |issue= 6 |pages= 643–6 |year= 2007 |pmid= 17374991 |doi=
* [http://www.aacr.org/home/public--media/for-the-media/fact-sheets/cancer-concepts/her2.aspx AACR Cancer Concepts Factsheet on HER2]
* [http://logikbase.com/website/techprofile.cfm?licid=1027 Her2/neu Vaccine Protects Against Tumor Growth ]
* [http://logikbase.com/website/techprofile.cfm?licid=618 Chimeric molecules and Methods of Use]
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Look at other dictionaries:
HER2/neu — Diagrama del trastuzumab (en azúl) unido al dominio extracelular de HER2/neu HUGO … Wikipedia Español
HER2/neu — Vorhandene Strukturdaten … Deutsch Wikipedia
HER2/neu — Human epidermal growth factor receptor 2. A protein involved in normal cell growth. It is found in high levels on some breast cancer cells. Also called human epidermal growth factor receptor 2 and c erbB 2 … English dictionary of cancer terms
HER2 — est une protéine. Le gène la codant est un proto oncogène appelé HER2/neu. Ce gène a été identifié au niveau du chromosome 17q21. Le terme HER2/neu signifie Human Epidermal Growth Factor Receptor 2 (récepteur pour les facteurs de croissance… … Wikipédia en Français
HER2 — HER2/neu Größe 1233 Aminosäuren Struktur Heterodimer; single pass Membranrezeptor Bezeichner … Deutsch Wikipedia
Neu (disambiguation) — Neu has several manings. It is the German word meaning new neu may refer to: The oncogene neu, see HER2/neu Neu may refer to: Neu, the common used symbol for neuraminic acid Neu (album), a Polysics album Neu!, a German krautrock band Neu Magazine … Wikipedia
HER2 — ErbB2 Комплекс между внеклеточным доменом HER2 (выделен кори … Википедия
ErbB-2 — HER2/neu Größe 1233 Aminosäuren Struktur Heterodimer; single pass Membranrezeptor Bezeichner … Deutsch Wikipedia
human epidermal growth factor receptor 2 — HER2/neu. A protein involved in normal cell growth. It is found in high levels on some breast cancer cells. Also called HER2/neu and c erbB 2 … English dictionary of cancer terms
Brustkrebs — Klassifikation nach ICD 10 C50 Mammakarzinom C50.0 Brustwarze und Warzenhof C50.1 … Deutsch Wikipedia