細胞対細胞のp53 ダイナミクスの変動は,分断的な殺戮につながります
Andrew L Paek1, Julia C Liu1, Alexander Loewer1
1Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|April 12, 2016
まとめ
化学療法の有効性は,部分的な癌細胞破壊によって制限されています. 固定された値ではなく,P53タンパク質のダイナミクスは,時間と抗アポプトシス遺伝子の発現に影響を受け,細胞死亡の確率を決定する.
科学分野:
- 分子生物学
- 癌 研究
- 細胞生物学
背景:
- 化学療法薬は,がん細胞の部分的な殺戮のために,しばしば限られた有効性を示します.
- 癌細胞の生存と死亡を制御するメカニズムを理解することは 治療結果を改善するために不可欠です
研究 の 目的:
- 化学療法で治療された結腸がん細胞の 分割殺傷における p53 タンパク質のダイナミクスの役割を調査する.
- 固定されたp53値が癌細胞死亡を決定するか,動的要因が関与するかを判断する.
主な方法:
- 生細胞画像は,化学療法中に結腸がん細胞のp53動態をモニターするために使用されました.
- 生き残った細胞と死にゆく細胞の両方のp53レベルとタイミングの定量分析が行われました.
主要な成果:
- 生き残った癌細胞と死にゆく癌細胞は,同じp53タンパク質レベルに達し,固定されたp53死亡の値を否定した.
- 細胞がアポトーシスを受ける確率は,p53レベルの持続時間と大きさの両方に依存していた.
- p53誘発のアポトーシスの値は,抗アポトーシス遺伝子,特にアポトーシス阻害剤 (IAP) 家族の薬剤依存性アップレギュレーションにより,時間とともに増加した.
結論:
- 化学療法への反応として起こる癌細胞死は,静的な値ではなく,p53タンパク質の運動に影響されるダイナミックなプロセスである.
- 抗アポプトシス遺伝子発現の時間的調節により,p53のアポプトシス値が調節され,治療への耐性が生じます.
- p53とIAPのような重要な分子プレーヤーのダイナミクスをモニタリングすることは,化学療法耐性を理解し,組み合わせ療法戦略を最適化するために不可欠です.
関連する概念動画
02:23Abnormal Proliferation
5.4K
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...
5.4K
02:36DNA Damage can Stall the Cell Cycle
10.3K
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...
10.3K
02:36DNA Damage Can Stall the Cell Cycle
3.3K
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...
3.3K
01:27Molecular Factors Affecting Cell Division
4.1K
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
4.1K
01:23Negative Regulator Molecules
38.8K
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.
38.8K
02:36Cells Coordinate Growth and Proliferation
5.3K
Cell size is a significant factor impacting cellular design, function, and fitness. There exists some internal coordination by which cells double their masses before division, thus, achieving homeostasis. Coordination between cell growth and proliferation depends on the checkpoints in between cell cycle phases. Loss of coordination or failure in the checkpoint mechanism can drive the cell to uncontrolled growth and loss of cellular function. Like dividing cells that coordinate cellular growth,...
5.3K