Biology of HER2 and its importance in breast cancer
Biology of HER2 and its importance in breast cancer
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DOI：
10.1159/000055396
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发表时间：
2001-01-01
期刊：
影响因子：
3.5
通讯作者：
Yarden, Y
中科院分区：
文献类型：
--
作者：
Yarden, Y
人表皮生长因子受体-2（HER 2/erbB 2）属于一个跨膜受体家族，参与调节细胞生长和分化的信号转导途径。HER 2的过表达/扩增与乳腺癌的恶性程度和不良预后相关。HER 2作为一种网络受体，介导癌细胞的信号传导，导致它们增殖。HER受体以单体形式存在，但在配体结合时二聚化。HER配体是二价生长因子分子，其低亲和力位点与HER 2结合。尚未鉴定出HER 2特异性配体，但HER 2是其他HER受体的优选异源二聚化配偶体。含HER 2的异二聚体是相对长寿命和有效的。HER 3没有固有活性，是HER 2的主要和最有效的二聚化伴侣。HER 2过表达使含HER 2的异源二聚体的形成偏向，导致对基质生长因子和致癌转化的反应性增强。从细胞表面去除HER 2或抑制其内在酶活性可降低致癌性。我们的研究表明，HER 2特异性抗体如赫赛汀（R）的抗肿瘤功效与其引导HER 2进入Cbl依赖性内吞和降解途径的能力有关。已报道的抗HER 2单克隆抗体在乳腺癌中的临床疗效突出了理解HER 2生物学的重要性。版权所有（C）2001 S. Karger AG，巴塞尔。
Human epidermal growth factor receptor-2 (HER2/erbB2) belongs to a family of four transmembrane receptors involved in signal transduction pathways that regulate cell growth and differentiation. Overexpression/amplification of HER2 is associated with malignancy and a poor prognosis in breast cancer. HER2 acts as a networking receptor that mediates signaling to cancer cells, causing them to proliferate. HER receptors exist as monomers but dimerize on ligand binding. HER ligands are bivalent growth factor molecules whose low-affinity site binds to HER2. No HER2-specific ligand has been identified but HER2 is the preferred heterodimerization partner for other HER receptors. HER2-containing heterodimers are relatively long-lived and potent. HER3 has no inherent activity and is the major and most potent dimerization partner of HER2. HER2 overexpression biases the formation of HER2-containing heterodimers, leading to enhanced responsiveness to stromal growth factors and oncogenic transformation. Removal of HER2 from the cell surface or inhibition of its intrinsic enzymatic activity may reduce oncogenicity. Our research suggests that the antitumor efficacy of HER2-specific antibodies such as Herceptin (R) relates to their ability to direct HER2 to a Cbl-dependent endocytosis and degradation pathway. The reported clinical therapeutic efficacy of anti-HER2 monoclonal antibodies in breast cancer highlights the importance of understanding the biology of HER2. Copyright (C) 2001 S. Karger AG, Basel.