Basic science of HER-2/neu: a review.
Basic science of HER-2/neu: a review.
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作者：
M. Hung;Y. Lau
HER-2/neu（也称为c-erbB-2）癌基因是表皮生长因子受体家族的第二个成员。它在许多不同类型的人类癌症中过表达，包括乳腺癌、卵巢癌、肺癌、胃癌和口腔癌。HER-2/neu在乳腺癌中的过表达与较差的总生存率相关，并且在临床前已显示其可增强恶性程度和转移表型。虽然不同的研究之间存在差异，HER-2/ neu过表达似乎在某些实验条件下诱导化疗耐药。许多研究令人信服地表明，HER-2/neu的抑制抑制HER-2/neu过表达的癌细胞的恶性表型。这些发现有力地表明HER-2/neu可以作为开发针对HER-2/neu过表达癌细胞的特异性抗癌药物的极好靶点。HER-2/neu编码的p185蛋白是一种受体酪氨酸激酶，可与多种信号转导途径相关。然而，目前尚不清楚特定的信号通路如何对应于特定的生物反应。本文综述了HER-2/neu受体酪氨酸激酶信号转导的基本信息，并总结了我们靶向HER-2/neu过表达癌细胞的方法。使用阳离子脂质体或腺病毒载体靶向HER-2/neu启动子，以将腺病毒-5 EIA基因产物和SV 40大T抗原的非转化突变体递送到荷瘤小鼠中。这导致肿瘤生长的抑制和生存期的延长。为了抑制HER-2/neu的功能，我们使用大黄素，一种酪氨酸激酶抑制剂。该药物可以抑制HER-2/neu的酪氨酸激酶活性，并优先阻断HER-2/neu过表达的人乳腺癌细胞在组织培养物中以及在裸鼠中的生长。
The HER-2/neu (also known as c-erbB-2) oncogene is the second member of the epidermal growth factor receptor family. It is overexpressed in many different types of human cancers, including breast, ovarian, lung, gastric, and oral cancers. Overexpression of HER-2/neu in breast cancer has been associated with poor overall survival and has been shown preclinically to enhance malignancy and the metastatic phenotypes. Although discrepancies exist between different studies, HER-2/ neu overexpression seems to induce chemoresistance in certain experimental conditions. Many studies have convincingly shown that repression of HER-2/neu suppresses the malignant phenotypes of HER-2/neu-overexpressing cancer cells. These findings strongly suggest that HER-2/neu may serve as an excellent target for developing anticancer agents specific for HER-2/neu-overexpressing cancer cells. HER-2/neu-encoded p185 protein is a receptor tyrosine kinase that can be associated with multiple signal transduction pathways. However, it is not yet clear how a specific signal pathway may correspond to a specific biological response. This report reviews basic information on signal transduction of HER-2/neu receptor tyrosine kinase and summarizes our approaches to targeting HER-2/neu-overexpressing cancer cells. The HER-2/neu promoter was targeted using cationic liposomes or an adenovirus vector to deliver the adenovirus-5 EIA gene products and a nontransformed mutant of the SV40 large T antigen into the tumor-bearing mice. This resulted in suppression of the tumor growth and prolongation of survival. For repressing the function of HER-2/neu we used emodin, a tyrosine kinase inhibitor. This agent can inhibit the tyrosine kinase activity of HER-2/neu and preferentially block the growth of the HER-2/neu-overexpressing human breast cancer cells in tissue culture as well as in nude mice.