通过DNA低甲基化抑制肠道瘤
P W Laird1, L Jackson-Grusby, A Fazeli
1Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142, USA.
Cell
|April 21, 1995
概括
减少DNA甲基转移酶活性显著降低了小鼠的肠道瘤. 这表明DNA甲基转移酶有助于瘤的发展,并可能在结直肠癌突变中发挥作用.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 癌症研究 癌症研究
背景情况:
- ApcMin小鼠是肠道瘤的一个模型.
- 在表观遗传调节中,DNA甲基转移酶 (DNMT) 的活性至关重要.
- DNMT在肠道瘤发展中的作用需要进一步阐明.
研究的目的:
- 为了研究DNA甲基转移酶活性降低对小鼠ApcMin诱导的肠道瘤的影响.
- 为了确定DNA低甲基化是否有助于瘤的发展.
主要方法:
- 在ApcMin小鼠中使用了基因修饰 (DNMT异性) 和药理抑制 (5-aza-deoxycytidine) 的组合.
- 量化了对照组和治疗组肠道腺瘤的数量.
主要成果:
- 在异子Min小鼠中减少DNMT活性导致肠腺瘤的急剧减少,从平均113个减少到仅2个息肉.
- 这突显了DNMT活动在这个模型中对瘤发展的实质性贡献.
结论:
- 在ApcMin小鼠模型中,DNA甲基转移酶活性在肠道瘤的发展中起着重要作用.
- 这些发现不支持DNA低甲基化的致癌作用.
- 结果与DNMT在产生人类结直肠癌中观察到的C到T转换中的作用一致.
相关概念视频
Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Loss of Tumor Suppressor Gene Functions
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
Loss of Tumor Suppressor Gene Functions
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...


