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

c-Myb 对成人结肠隐窝稳态的调节和结肠癌转移基因的激活

• 批准号: nhmrc : 145649
• 负责人: Prof Robert Ramsay
• 金额: $ 44.42万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/regulation-adult-colonic-c-myb/82288
• 关键词: Regulation; adult; colonic; crypt; homeostasis

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.

正常结肠生物学的调节和涉及结肠癌的基因的激活c-myb基因对于血液系统和结肠的正常生物学是必需的。该基因参与调节新细胞的产生与它们完成指定任务后及时清除之间的平衡。有大量的证据支持c-myb在血液系统调节中的作用。我们认为，控制拥有健康血液系统所需的大量细胞产生的规则与结肠所使用的规则相似，如果不是完全相同的话。这是因为结肠也产生大量的细胞，每个细胞都有特殊的任务和几天的定义寿命。正是这种细胞数量的快速扩张和细胞的程序化短寿命需要多重控制和非常严格的调节。此外，如果这一过程被破坏这些控制的遗传变化所劫持，那么就有许多机会引发和加剧恶性变化或癌症。该项目研究了相同基因在两种情况下的作用。首先，当基因以正常的高度调节的水平表达时，与结肠的正常生物学相关。第二种情况是当这些基因被允许过度表达，从而驱动过程更长或在不适当的情况下导致恶性生长。