Brandt-Rauf P W, Pincus M R, Carney W P
Department of Medicine and Comprehensive Cancer Center, Columbia University, New York, N.Y. 10032.
Crit Rev Oncog. 1994;5(2-3):313-29. doi: 10.1615/critrevoncog.v5.i2-3.100.
The c-erbB-2 (HER-2, neu) oncogene has been implicated frequently in many human tumors. This oncogene codes for a 185-kDa protein that functions as a transmembrane growth factor receptor. Overexpression of the normal protein or point mutations in the transmembrane domain of the protein have been shown to have a transforming effect. Molecular structure studies of the transmembrane domain provide a plausible explanation for this transforming effect in both cases and relate this to the process of receptor dimerization in the membrane, degradation of the protein with release of the extracellular domain (ECD) into the extracellular environment, and aberrant signal transduction. The release of the ECD into the extracellular environment provides a potential biomarker for the study of signal transduction at the molecular level in vivo. The ECD can be quantitated immunologically in the serum of individuals with cancers associated with p185 overexpression and in individuals at risk for the development of such cancers and can be used to distinguish these individuals from normal, healthy controls. Identification of such individuals by their serum ECD levels combined with specific chemotherapeutic/chemoprophylactic interventions could allow for improvement treatment and prevention of c-erbB-2-related cancers.
c-erbB-2（HER-2，neu）癌基因在许多人类肿瘤中频繁出现。该癌基因编码一种185 kDa的蛋白质，其作为跨膜生长因子受体发挥作用。已表明正常蛋白质的过表达或该蛋白质跨膜结构域中的点突变具有转化作用。跨膜结构域的分子结构研究为这两种情况下的这种转化作用提供了合理的解释，并将其与膜中受体二聚化过程、蛋白质降解以及细胞外结构域（ECD）释放到细胞外环境中以及异常信号转导联系起来。ECD释放到细胞外环境中为体内分子水平信号转导研究提供了一种潜在的生物标志物。可以通过免疫方法在与p185过表达相关的癌症患者血清以及有患此类癌症风险的个体血清中对ECD进行定量，并且可用于将这些个体与正常健康对照区分开来。通过血清ECD水平识别此类个体并结合特定的化疗/化学预防干预措施，可能会改善c-erbB-2相关癌症的治疗和预防。
