在炎症相关的癌症中,NF-kappaB作为瘤促进剂起作用
Eli Pikarsky1, Rinnat M Porat, Ilan Stein
1Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel. peli@hadassah.org.il
Nature
|August 27, 2004
概括
慢性炎症有助于癌症的发展. 核因子kappaB (NF-kappaB) 的激活对于与炎症相关的癌症进展至关重要,使其成为预防的潜在治疗点.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 肝病学 肝病学是一种肝病学.
背景情况:
- 慢性炎症与大约20%的人类癌症有关,但其机制尚不清楚.
- 核因子kappaB (NF-kappaB) 激活是经常在瘤中发现的关键炎症反应.
- 在将炎症与癌症联系起来,NF-kappaB的作用需要进一步阐明.
研究的目的:
- 研究NF-kappaB在与炎症相关的肝细胞癌发展中的作用.
- 确定NF-kappaB是否是慢性肝炎向肝癌进展的关键调解者.
主要方法:
- 利用Mdr2-淘汰赛小鼠,作为自发胆固醇性肝炎和肝细胞癌的模型.
- 监测肝炎和癌症进展,评估NF-kappaB通过瘤缩因子-alpha (TNFalpha) 的激活.
- 在不同疾病阶段通过抑制NF-kappaB使用肝细胞特异的可诱导IkappaB-超抑制器转基因和抗TNFalpha治疗进行干预.
主要成果:
- 肝细胞中的NF-kappaB激活是由TNFalpha.通过炎症触发的.
- 早期NF-kappaB抑制 (出生至7个月) 没有影响肝炎或早期转化.
- 晚期NF-kappaB抑制导致转化肝细胞的亡,并防止肝细胞癌的发展.
结论:
- NF-kappaB对于炎症相关癌症的进展至关重要.
- 准NF-kappaB可能为慢性炎症疾病的癌症预防提供一种策略.
- 抑制NF-kappaB的时间对于预防瘤进展的治疗疗效至关重要.
相关概念视频
The Nucleolus
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
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...
Cancer-Critical Genes I: Proto-oncogenes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
The Intrinsic Apoptotic Pathway
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...
NF-kB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...


