Clark G J, Der C J
Department of Pharmacology, University of North Carolina at Chapel Hill 27599, USA.
Breast Cancer Res Treat. 1995 Jul;35(1):133-44. doi: 10.1007/BF00694753.
Although ras mutations are infrequent (approximately 5%) in breast cancers, there is considerable evidence that suggests that the pathways which Ras services may still be deregulated in breast cancer cells. The recent identification of many of the components of the Ras signal transduction pathway has defined a network of proto-oncogene proteins controlling diverse signaling events that regulate cell growth and differentiation. Consequently, mutations that perturb the function of any one component of this signal pathway may trigger the same oncogenic events as mutation of ras itself. Moreover, several Ras-related proteins have recently been demonstrated to possess the ability to trigger malignant transformation via signaling pathways shared with Ras proteins. Thus, it is possible that the aberrant function of Ras-related proteins may contribute to breast cancer development. Consequently, it is important not to dismiss the Ras pathway in the development of breast cancer merely because of the infrequent detection of mutations in ras itself, but rather to consider the influence of aberrations upstream or downstream of Ras and of certain Ras-related proteins in the development of breast cancer. Finally, the critical importance of components upstream and downstream of Ras provides additional targets for rational drug design approaches to block the aberrant function of Ras signaling in human tumors.
尽管Ras突变在乳腺癌中并不常见（约5%），但有大量证据表明，Ras所参与的信号通路在乳腺癌细胞中仍可能失调。最近对Ras信号转导通路中许多成分的鉴定，确定了一个原癌基因蛋白网络，该网络控制着调节细胞生长和分化的各种信号事件。因此，干扰该信号通路中任何一个成分功能的突变，可能会引发与Ras自身突变相同的致癌事件。此外，最近有几种Ras相关蛋白被证明能够通过与Ras蛋白共享的信号通路触发恶性转化。因此，Ras相关蛋白的异常功能可能促成乳腺癌的发展。因此，重要的是不要仅仅因为在Ras本身中很少检测到突变，就忽视Ras信号通路在乳腺癌发展中的作用，而应考虑Ras上下游的异常以及某些Ras相关蛋白在乳腺癌发展中的影响。最后，Ras上下游成分的关键重要性为合理的药物设计方法提供了额外的靶点，以阻断人类肿瘤中Ras信号的异常功能。
