Regulation of adult colonic crypt homeostasis and activation of colon cancer metastasis genes by c-Myb

调节正常的结肠生物学和激活与结肠癌相关的基因c-myb基因对于血液系统和结肠的正常生物学是必不可少的。这种基因参与调节新细胞的产生和它们完成指定任务后及时清除之间的平衡。有大量证据支持c-myb在调节血液系统中的作用。我们认为，管理拥有健康血液系统所需的大量细胞生产的规则与结肠使用的规则相似，如果不是相同的话。这是因为结肠还会产生大量的细胞，每个细胞都有特殊的任务和几天的固定寿命。正是这种细胞数量的快速扩张和细胞程序化的短暂寿命，需要进行多重控制和非常严格的监管。此外，如果这一过程被破坏这些控制的基因变化所劫持，那么就有许多机会启动和加强恶变或癌症。这个项目考察了相同基因在两种情况下的作用。首先，当基因在正常的、高度调控的水平上表达时，这些基因与正常的结肠生物学有关。第二个背景是当这些基因被允许过度表达，从而驱动过程更长时间或在不适当的情况下导致恶性生长。

Regulation of normal colon biology and activation of genes involved colon cancer The c-myb gene is essential for the normal biology of the blood system and the colon. This gene is involved in regulating the balance between the production of new cells and their timely removal once they have completed their assigned tasks. There is a large body of evidence that supports the role of c-myb in the regulation of the blood system. We believe that the rules that govern the production of the huge number of cells needed to have a healthy blood system are similar if not identical to the rules used by the colon. This is because the colon also produces a massive number of cells each with special tasks and a defined life span of a few days. It is this rapid expansion of cell numbers and the programmed short life span of cells that necessitates multiple controls and very tight regulation. Furthermore if this process is hijacked by genetic changes that undermine these controls then there are numerous opportunities to initiate and potentiate malignant change or cancer. This project examines the role of the same genes in two contexts. Firstly when the genes are expressed at normal, highly regulated levels associated with the normal biology of the colon. The second context is when these genes are permitted to be over-expressed and thus drive processes for longer or in inappropriate situations leading to malignant growth.