Modeling cell cycle control and cancer with pRB tumor suppressor.
Modeling cell cycle control and cancer with pRB tumor suppressor.
复制标题
使用 pRB 肿瘤抑制因子模拟细胞周期控制和癌症。
DOI：
10.1007/b136682
复制
发表时间：
2006
影响因子：
--
通讯作者：
Yamasaki,Lili
中科院分区：
文献类型：
--
作者：
Yamasaki,Lili
癌症是一种复杂的疾病综合症，其特征是细胞数量增加，破坏生物体内的正常组织结构。定义一种癌症的普遍机制并希望设计出一种对抗癌症的灵丹妙药是不可能的，很大程度上是因为不同类型的癌症和不同个体之间存在很大的差异。然而，在过去的几十年里，我们已经了解到很多关于正常细胞癌变的不同过程，以及癌基因和肿瘤抑制基因之间的微妙平衡被破坏，有利于肿瘤细胞的生长和存活。癌症发展最重要的细胞障碍之一是视网膜母细胞瘤肿瘤抑制 (pRB) 通路，该通路在多种人类肿瘤中失活，并通过抑制 E2F/DP 转录因子家族来控制细胞周期进程。我们对pRB抑制肿瘤的看法之所以清晰，很大程度上是因为我们相信细胞周期的普遍性，以及我们对体内肿瘤途径建模的尝试，这一点最明显的是来自突变小鼠模型的大量数据，这些模型被设计用于了解细胞周期调节因子如何限制体内生长以及这些调节因子的放松调节如何促进癌症的发展。尽管情况如此清晰，但我们在过去两年中难以置信地目睹了一些令人震惊的结果，这些结果挑战了细胞周期范式的基础，并使我们认真质疑这些细胞周期调节剂实际上有多重要。
Cancer is a complex syndrome of diseases characterized by the increased abundance of cells that disrupts the normal tissue architecture within an organism. Defining one universal mechanism underlying cancer with the hope of designing a magic bullet against cancer is impossible, largely because there is so much variation between various types of cancer and different individuals. However, we have learned much in past decades about different journeys that a normal cell takes to become cancerous, and that the delicate balance between oncogenes and tumor suppressor is upset, favoring growth and survival of the tumor cell. One of the most important cellular barriers to cancer development is the retinoblastoma tumor suppressor (pRB) pathway, which is inactivated in a wide range of human tumors and controls cell cycle progression via repression of the E2F/DP transcription factor family. Much of the clarity with which we view tumor suppression via pRB is due to our belief in the universality of the cell cycle and our attempts to model tumor pathways in vivo, nowhere so evident as in the multitude of data emerging from mutant mouse models that have been engineered to understand how cell cycle regulators limit growth in vivo and how deregulation of these regulators facilitates cancer development. In spite of this clarity, we have witnessed with incredulity several stunning results in the last 2 years that have challenged the very foundations of the cell cycle paradigm and made us question seriously how important these cell cycle regulators actually are.