Greer Peter A, Kanda Shigeru, Smithgall Thomas E
Department of Pathology and Molecular Medicine, Queen's University, Division of Cancer Biology and Genetics, Queen's Cancer Research Institute, Kingston, Ontario, Canada.
Front Biosci (Schol Ed). 2012 Jan 1;4(2):489-501. doi: 10.2741/280.
The FES gene was first discovered as a protein-tyrosine kinase-encoding retroviral oncogene. The ability of v-FES to transform cells in vitro and initiate cancer in vivo has been established by cell culture, engraftment and transgenic mouse studies. The corresponding cellular c-FES proto-oncogene encodes a cytoplasmic FES protein-tyrosine kinase with restrained catalytic activity relative to its retrovirally encoded homologs. These observations have stimulated a search for mutations or inappropriate expression of c-FES in human cancers and research aimed at understanding the functions of the FES kinase and its potential involvement in cancer and other diseases. Paradoxically, although first identified as an oncogene, genetic evidence has also implicated c-fes as a potential tumor suppressor. This review will describe observations from basic and translational research which shapes our current understanding of the physiological, cellular and molecular functions of the FES protein-tyrosine kinase and its potential roles in tumorigenesis. We also propose a model to reconcile the conflicting oncogenic and tumor suppressor roles of c-FES in tumorigenesis.
FES基因最初是作为一种编码蛋白酪氨酸激酶的逆转录病毒致癌基因被发现的。通过细胞培养、移植和转基因小鼠研究，已证实v-FES在体外转化细胞和在体内引发癌症的能力。相应的细胞c-FES原癌基因编码一种细胞质FES蛋白酪氨酸激酶，相对于其逆转录病毒编码的同源物，其催化活性受到抑制。这些观察结果激发了人们对人类癌症中c-FES突变或异常表达的研究，以及旨在了解FES激酶功能及其在癌症和其他疾病中潜在作用的研究。矛盾的是，尽管c-FES最初被鉴定为致癌基因，但遗传学证据也表明它可能是一种潜在的肿瘤抑制因子。本综述将描述基础研究和转化研究的观察结果，这些结果塑造了我们目前对FES蛋白酪氨酸激酶的生理、细胞和分子功能及其在肿瘤发生中潜在作用的理解。我们还提出了一个模型，以协调c-FES在肿瘤发生中相互矛盾的致癌和肿瘤抑制作用。
