Everything about Her2 Neu totally explained
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| Name = V-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)
| HGNCid = 3430
| Symbol = ERBB2
| AltSymbols =; HER-2; HER-2/neu; HER2; NEU; NGL; TKR1; c-erb B2
| OMIM = 164870
| ECnumber =
| Homologene = 3273
| MGIid = 95410
| GeneAtlas_image1 = PBB_GE_ERBB2_216836_s_at.png
| GeneAtlas_image2 = PBB_GE_ERBB2_210930_s_at.png
| DateOfBotUpdate = 23:27, 14 September 2007 (UTC)
| Function =
| Component =
| Process =
| Orthologs =
}}
HER2/neu (also known as ErbB-2, ) 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).
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. The
HER2 gene is a
proto-oncogene located 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. 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 for example 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 .
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 (External Link
), which inhibits dimerization of HER2 and HER3 receptors, is in advanced clinical trials.
Further Information
Get more info on 'Her2 Neu'.
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