Department of Forensic Medicine and Toxicology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Histol Histopathol. 2012 Jun;27(6):677-92. doi: 10.14670/HH-27.677.
Src, a 60 kDa non-receptor tyrosine kinase, is the product of normal c-src of the human genome and member of the Src protein tyrosine kinases family (SFK). As described by Martin and Rous, a genetic recombination between c-src and the RSV oncogene of Rous sarcoma virus results in a modified Src protein, with increased intrinsic activity and transforming potential in animal and human tissues. Several in vitro and in vivo studies supported this theory providing insight in the signalling pathways involved. Accumulating evidence from studies on clinical samples supported the role of Src in the process of carcinogenesis and disease progression in several human malignancies. Some studies have further reinforced the significance of the kinase in malignacy by correlating its expression and/or activity with important clinicopathological parameters, such as tumour stage, histopathological grade, proliferative capacity and most importantly patient's survival. This review is a comprehensive report of the published evidence on the expression and clinical significance of Src in human malignancy, which constitutes the background of the current studies and clinical trials on the use of Src inhibitors as novel potent antineoplastic strategy.
Src 是一种 60 kDa 的非受体酪氨酸激酶,是人类基因组中正常 c-src 的产物,也是 Src 蛋白酪氨酸激酶家族(SFK)的成员。正如 Martin 和 Rous 所描述的,c-src 与 Rous 肉瘤病毒的 RSV 致癌基因之间的基因重组导致了一种改良的 Src 蛋白,在动物和人体组织中具有更高的内在活性和转化潜能。一些体外和体内研究支持了这一理论,为相关信号通路提供了深入的了解。来自临床样本的研究证据越来越多地支持 Src 在多种人类恶性肿瘤的致癌和疾病进展过程中的作用。一些研究通过将其表达和/或活性与重要的临床病理参数(如肿瘤分期、组织病理学分级、增殖能力,最重要的是患者的生存)相关联,进一步强调了激酶在恶性肿瘤中的重要性。本综述全面报告了 Src 在人类恶性肿瘤中的表达和临床意义的已发表证据,这构成了当前 Src 抑制剂作为新型抗肿瘤策略的研究和临床试验的背景。