相关实验视频
Updated: Jul 2, 2025

06:53
Quantification of γH2AX Foci in Response to Ionising Radiation
Published on: April 6, 2010
20.5K
对于瘤生长而言,需要DNA损伤信号组 histone H2AX
Lizbeth Contreras1, Lorena García-Gaipo1, Berta Casar2,3
1Cell cycle, Stem Cell Fate and Cancer Laboratory, Institute for Research Marqués de Valdecilla (IDIVAL), 39011, Santander, Spain.
Cell death discovery
|February 24, 2024
概括
这项研究揭示,虽然基因素 γH2AX ( H2AX) 对于DNA修复和组织平衡至关重要,但它的缺失令人惊地减少了癌症的发展. 这表明γH2AX在维持健康组织和促进瘤发生方面发挥了复杂的作用.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 皮肤病学 皮肤病学
背景情况:
- 癌症通常发生在易受DNA损伤的自我更新组织中.
- 基因 γH2AX ( H2AX) 对于DNA修复和基因组稳定性至关重要.
- 在癌症发育中的γH2AX的特定作用仍然在很大程度上是未知的.
研究的目的:
- 调查gH2AX在表皮平衡和癌症开始中的功能.
- 确定H2AX基因沉默对皮肤组织和致癌性的影响.
主要方法:
- 使用了缺少H2AX基因的淘汰赛 (KO) 鼠标模型.
- 检查了表皮组织的细胞循环活性,DNA修复效率和增生.
- 评估了突变物诱导的皮肤癌发育和特征瘤特性.
- 分析的干细胞标志物表达 (Δp63).
主要成果:
- 缺少H2AX导致细胞循环失调,DNA修复受损,表皮增生.
- 缺乏H2AX的小鼠表现出显著减少的突变原诱导瘤形成,瘤出现较晚,更少,更小,更少恶性.
- 干细胞标记物Δp63在H2AX缺乏的表皮中显著降低.
结论:
- H2AX对于维持组织平衡和皮肤上适当的干细胞功能至关重要.
- 尽管H2AX在DNA修复中的作用很大,但矛盾的是,H2AX对于癌症的发展是必需的.
- 这些发现凸显了H2AX在组织维护和瘤发生中的双重作用,挑战了它作为仅仅瘤抑制剂的传统观点.
相关概念视频
DNA Damage can Stall the Cell Cycle
9.2K
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...
9.2K
Abnormal Proliferation
4.5K
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...
4.5K
The Intrinsic Apoptotic Pathway
6.5K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.5K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
Nucleotide Excision Repair
3.5K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.5K
PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K

