Slamon D J, Godolphin W, Jones L A, Holt J A, Wong S G, Keith D E, Levin W J, Stuart S G, Udove J, Ullrich A
Department of Medicine, U.C.L.A. School of Medicine 90024.
Science. 1989 May 12;244(4905):707-12. doi: 10.1126/science.2470152.
Carcinoma of the breast and ovary account for one-third of all cancers occurring in women and together are responsible for approximately one-quarter of cancer-related deaths in females. The HER-2/neu proto-oncogene is amplified in 25 to 30 percent of human primary breast cancers and this alteration is associated with disease behavior. In this report, several similarities were found in the biology of HER-2/neu in breast and ovarian cancer, including a similar incidence of amplification, a direct correlation between amplification and over-expression, evidence of tumors in which overexpression occurs without amplification, and the association between gene alteration and clinical outcome. A comprehensive study of the gene and its products (RNA and protein) was simultaneously performed on a large number of both tumor types. This analysis identified several potential shortcomings of the various methods used to evaluate HER-2/neu in these diseases (Southern, Northern, and Western blots, and immunohistochemistry) and provided information regarding considerations that should be addressed when studying a gene or gene product in human tissue. The data presented further support the concept that the HER-2/neu gene may be involved in the pathogenesis of some human cancers.
乳腺癌和卵巢癌占女性所患癌症总数的三分之一，二者合计约占女性癌症相关死亡人数的四分之一。HER-2/neu原癌基因在25%至30%的人类原发性乳腺癌中呈扩增状态，且这种改变与疾病行为相关。在本报告中，发现HER-2/neu在乳腺癌和卵巢癌生物学特性方面存在若干相似之处，包括相似的扩增发生率、扩增与过表达之间的直接关联、无扩增情况下出现过表达的肿瘤证据，以及基因改变与临床结局之间的关联。同时对大量这两种肿瘤类型进行了该基因及其产物（RNA和蛋白质）的全面研究。该分析确定了用于评估这些疾病中HER-2/neu的各种方法（Southern印迹法、Northern印迹法、Western印迹法和免疫组织化学）存在的若干潜在缺陷，并提供了有关在人体组织中研究基因或基因产物时应考虑因素的信息。所呈现的数据进一步支持了HER-2/neu基因可能参与某些人类癌症发病机制的观点。
