The basic biology of HER2
The basic biology of HER2
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DOI：
10.1023/a:1011195320446
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发表时间：
2001-01-01
影响因子：
50.5
通讯作者：
Yarden, Y
中科院分区：
文献类型：
--
作者：
Rubin, I;Yarden, Y
人表皮生长因子受体（HER/erbB）是一个由四种细胞表面受体组成的家族，参与控制正常细胞生长和分化的信号传递。一系列的生长因子作为配体，但没有一个是特异性的HER 2受体。HER受体以单体和二聚体（同源或异源二聚体）存在。与HER 1、HER 3或HER 4结合的配体诱导受体快速二聚化，并明显偏好HER 2作为二聚体伴侣。此外，含HER 2的异二聚体产生的细胞内信号显著强于其他HER组合发出的信号。在正常细胞中，很少有HER 2分子存在于细胞表面，因此很少形成异二聚体，生长信号相对较弱且可控。当HER 2过表达时，形成多个HER 2异二聚体，细胞信号传导更强，导致对生长因子的反应性增强和恶性生长。这解释了为什么HER 2过表达是乳腺肿瘤预后不良的指标，并可能预测对治疗的反应。HER 2是一种高度特异性和有前途的新乳腺癌治疗靶点。重组人抗HER 2单克隆抗体（rhuMAb-HER 2、曲妥珠单抗、赫赛汀）诱导HER 2从细胞表面快速清除，从而降低其对异二聚体的利用度并降低致癌性。
Human epidermal growth factor receptors (HER/erbB) constitute a family of four cell surface receptors involved in transmission of signals controlling normal cell growth and differentiation. A range of growth factors serve as ligands, but none is specific for the HER2 receptor. HER receptors exist as both monomers and dimers, either homo- or heterodimers. Ligand binding to HER1, HER3 or HER4 induces rapid receptor dimerization, with a marked preference for HER2 as a dimer partner. Moreover, HER2-containing heterodimers generate intracellular signals that are significantly stronger than signals emanating from other HER combinations. In normal cells, few HER2 molecules exist at the cell surface, so few heterodimers are formed and growth signals are relatively weak and controllable. When HER2 is overexpressed multiple HER2 heterodimers are formed and cell signaling is stronger, resulting in enhanced responsiveness to growth factors and malignant growth. This explains why HER2 overexpression is an indicator of poor prognosis in breast tumors and may be predictive of response to treatment. HER2 is a highly specific and promising target for new breast cancer treatments. The recombinant human anti-HER2 monoclonal antibody (rhuMAb-HER2, trastuzumab, Herceptin) induces rapid removal of HER2 from the cell surface, thereby reducing its availability to heterodimers and reducing oncogenicity.