DNAヒポメチル化による腸内腫瘍の抑制
P W Laird1, L Jackson-Grusby, A Fazeli
1Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142, USA.
Cell
|April 21, 1995
まとめ
DNAメチルトランスフェラーゼの活性を減少させることで,マウスの腸内腫瘍が著しく減少しました. これは,DNAメチルトランスフェラーゼが腫瘍発育に寄与し,大腸がんの変異に役割を果たす可能性があることを示唆しています.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
- がん研究 がん研究
背景:
- ApcMinマウスは腸内腫瘍症のモデルである.
- DNAメチルトランスフェラーゼ (DNMT) の活動は,表遺伝的調節において極めて重要です.
- 腸内腫瘍の発達におけるDNMTの役割については,さらなる解明が必要である.
研究 の 目的:
- マウスにおけるApcMin誘発の腸内腫瘍に減少したDNAメチルトランスフェラーゼ活性が与える影響を調査する.
- DNAヒポメチル化が腫瘍発育に寄与するかどうかを判断する.
主な方法:
- ApcMinマウスの遺伝子改変 (DNMTヘテロジゴシティ) と薬理学的抑制 (5-アザ-デオキシチチジン) の組み合わせを使用した.
- 治療群と対照群の腸腺腫の数を定量化しました.
主要な成果:
- ヘテロジゴートMinマウスにおけるDNMTの活性低下は,腸内アデノマの劇的な減少につながり,平均113からわずか2つのポリプに減少しました.
- これは,このモデルにおける腫瘍発育に対するDNMT活動の実質的な貢献を強調しています.
結論:
- DNAメチルトランスフェラーゼの活動は,ApcMinマウスモデルにおける腸内腫瘍の発生に重要な役割を果たしています.
- この発見は,DNA低甲基化の腫瘍性作用を支持するものではありません.
- 結果は,ヒトの結腸直腸がんで観察されたCからTへの移行を生成するDNMTの役割と一致しています.
関連する概念動画
01:46Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
02:23Abnormal 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...
01:12Loss 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...
01:37Epigenetic 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...
01:12Loss 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...
01:12Role 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...