Targeting distinct apoptotic pathways in mammary gland involution

针对乳腺退化中不同的细胞凋亡途径

• 批准号: BB/D012937/1
• 负责人: Christine Watson
• 金额: $ 29.64万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD012937%2F1
• 关键词: Targeting; distinct; apoptotic; pathways; mammary

Cells grow and divide to produce more cells. During growth of an embryo, certain cells have to be removed for proper function in the adult animal. An interesting example is seen in limb development. Ducks have webbed feet but human embryos also have webbed fingers and toes before they are born. The skin cells between the digits is removed by inducing them to die. This is a normal process. However, sometimes things go wrong and either too many cells, or the wrong type of cells, are made. Occasionally also, mistakes are made in copying the cell's DNA and this could cause cancer to develop. In order to eliminate this problem, and to remove normal cells that are no longer required, all cells have acquired the ability to kill themselves by activating a series of steps that result in the components of the cell being dismantled and packaged into small fragments. This cellular debris is then eaten up, or engulfed, by professional phagocytes whose job is to remove dead cells and clear away debris to prevent further damage to the surrounding tissue. This is called programmed cell death, or apoptosis. Apoptosis is very important in the lactating breast where it is needed to remove the milk producing cells when the baby is weaned and no longer needs breast feeding. We have been studying the apoptotic events that take place in breast cells and how these are controlled. We have found that the transcription factor Stat6, which binds to DNA to induce transcription of specific genes, is important for initiating apoptosis. In this project, we aim to identify genes are controlled by Stat6 and how they are involved in killing mammary cells.

细胞生长并分裂以产生更多细胞。在胚胎生长过程中，必须去除某些细胞才能在成年动物中发挥正常功能。一个有趣的例子是肢体发育。鸭子的脚有蹼，但人类胚胎在出生前也有蹼的手指和脚趾。通过诱导死亡来去除手指之间的皮肤细胞。这是一个正常的过程。然而，有时会出现问题，要么产生太多细胞，要么产生错误类型的细胞。有时，复制细胞 DNA 时也会出现错误，这可能会导致癌症的发生。为了消除这个问题，并去除不再需要的正常细胞，所有细胞都获得了自杀的能力，通过激活一系列步骤，导致细胞的成分被分解并包装成小碎片。然后，这些细胞碎片被专业吞噬细胞吃掉或吞没，吞噬细胞的作用是去除死亡细胞并清除碎片，以防止对周围组织的进一步损害。这称为程序性细胞死亡或细胞凋亡。细胞凋亡在哺乳期乳房中非常重要，当婴儿断奶并且不再需要母乳喂养时，需要清除产奶细胞。我们一直在研究乳腺细胞中发生的凋亡事件以及如何控制这些事件。我们发现转录因子 Stat6 与 DNA 结合诱导特定基因的转录，对于启动细胞凋亡非常重要。在这个项目中，我们的目标是确定由 Stat6 控制的基因以及它们如何参与杀死乳腺细胞。

项目成果

Cytokine signalling in mammary gland development.

乳腺发育中的细胞因子信号传导。

• DOI: 10.1016/j.jri.2010.11.006
• 发表时间: 2011
• 期刊: Journal of reproductive immunology
• 影响因子: 3.4
• 作者: Watson CJ