テトラプロイドを生成するサイトキネーシスの失敗は,p53-null細胞の腫瘍発生を促進する
Takeshi Fujiwara1, Madhavi Bandi, Masayuki Nitta
1Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|October 14, 2005
まとめ
細胞分裂の失敗はテトラプロイド細胞を作り,遺伝的不安定性と癌を促進します. テトラプロイド細胞は,二倍細胞ではありませんが,四倍プロイド性を示し,悪性乳腺腫瘍に発展しました.
科学分野:
- 腫瘍学 腫瘍学
- 細胞生物学 細胞生物学
- 遺伝学 遺伝学とは
背景:
- 腫瘍発生は,遺伝的に不安定なテトラプロイド細胞につながる細胞分裂の失敗を含むと仮定されています.
- テトラプロイド細胞は,アヌプロイド性悪性腫瘍の発生を促進する可能性があります.
研究 の 目的:
- 細胞分裂の失敗と,その後の四分化が腫瘍形成を促進するという仮説を検証する.
- 染色体不安定性と悪性変異におけるテトラプロイドの役割を調査する.
主な方法:
- p53-null マウス乳腺上皮細胞 (MMECs) の細胞運動を一時的に阻害し,二倍体と四倍体培養物を分離する.
- 染色体の不安定性 (不適切な分離,再配置) を評価する.
- 発癌物質への曝露後の in vitro 変容と,裸のマウスへの皮下移植後の in vivo 腫瘍発生性を評価する.
主要な成果:
- テトラプロイド型MMECは,二倍型細胞と比較して,全染色体の誤差分離と染色体の再編成の増加を示した.
- 発癌物質に曝露された後,テトラプロイド細胞のみが in vitro 変異を経験した.
- 移植されたテトラプロイド細胞は,二プロイド細胞ではないが,トランスロケーションとマトリックスメタルプロテインアース (MMP) 遺伝子増幅によって特徴づけられる悪性乳腺上皮がんを形成した.
結論:
- テトラプロイジは,p53-null MMECsにおける染色体変異の頻度を著しく増加させる.
- テトラプロイジは,悪性乳腺上皮がんの発症を促進する重要な要因です.
- この発見は,細胞分裂不全,四分化,腫瘍発生を結びつける長年の仮説を裏付けている.
関連する概念動画
01:23Negative Regulator Molecules
32.1K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
32.1K
02:36DNA Damage can Stall the Cell Cycle
8.5K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
8.5K
02:39Positive Regulator Molecules
5.3K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.3K
02:34Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
02:23Abnormal Proliferation
4.0K
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...
4.0K
02:36DNA Damage Can Stall the Cell Cycle
2.4K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
2.4K