Davies Alastair H, Dunn Sandra E
Laboratory of Oncogenomic Research, Departments of Pediatrics and Experimental Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada.
Oncotarget. 2011 May;2(5):401-6. doi: 10.18632/oncotarget.276.
Surprisingly little is known about the underlying genetic events that trigger the progression of a normal cell into a cancerous cell. We recently developed a YB-1-driven model of pre-malignancy where we uncovered that the oncogene promotes genomic instability through cell cycle checkpoint slippage and centrosome amplification. In this research perspective, we describe a possible mechanism by which YB-1 instigates preneoplastic transformation. Using Kinex antibody microarrays with coverage of 800 proteins, we discovered that pre-malignant cells exhibit deregulated signal transduction along the HER2-MAPK-RSK axis. We will discuss the implications of these finding in regard to early intervention strategies.
令人惊讶的是,对于触发正常细胞转变为癌细胞的潜在基因事件,我们所知甚少。我们最近开发了一种由YB-1驱动的癌前病变模型,在此模型中我们发现该癌基因通过细胞周期检查点滑脱和中心体扩增促进基因组不稳定。在本研究展望中,我们描述了YB-1引发肿瘤前转化的一种可能机制。通过使用覆盖800种蛋白质的Kinex抗体微阵列,我们发现癌前细胞在HER2-MAPK-RSK轴上表现出信号转导失调。我们将讨论这些发现对于早期干预策略的意义。