致癌性BRAF针对肺和甲状腺的组织特异性通过共享的血统因子
Elin Schoultz1,2, Shawn Liang1,2, Therese Carlsson1,2
1Sahlgrenska Center for Cancer Research, University of Gothenburg, Göteborg, Sweden.
iScience
|August 3, 2023
概括
肺部和甲状腺组织之间的癌症发育不同,即使具有相似的遗传突变. 像NKX2-1这样的谱系转录因子会影响Braf突变如何驱动瘤生长和器官特异性.
科学领域:
- 在瘤学瘤学.
- 发展生物学 发展生物学
- 遗传学 遗传学 是一个
背景情况:
- 癌细胞的起源决定了瘤的表型.
- 瘤发生的组织特异性受到血统转录因子的影响,但对于具有类似发育特征的器官来说,这一点尚不清楚.
研究的目的:
- 调查血统定义的转录因子如何影响组织特异性瘤发生.
- 为了比较Braf突变后肺和甲状腺组织的瘤发育和进展.
主要方法:
- 使用了为Braf.使用的异构合的Nkx2.1CreER小鼠.
- 用于诱导瘤基因激活的托莫西芬.
- 通过变异性等位基序测序分析了瘤发育,潜伏和Braf激活.
- 在瘤进展期间评估肺和甲状腺细胞中的NKX2-1表达.
主要成果:
- Nkx2.1CreER;Braf突变者自发地迅速 (1-3个月) 发展出肺腺癌.
- 甲状腺瘤是罕见的和较小,尽管类似的布拉夫激活水平.
- 诱导的瘤基因激活加速了肺部瘤的生长,但不是甲状腺瘤的生长.
- 肺和甲状腺细胞都在早期瘤阶段暂时降低NKX2-1的调节.
结论:
- BRAF V600E诱导的瘤发生表现出特定器官的特征.
- 这些器官特异性特征可以通过共享的血统因子 (如NKX2-1) 进行差异调节.
- 血统转录因子在确定癌症发展的组织特异性方面发挥着关键作用.
更多相关视频
相关概念视频
Targeted Cancer Therapies
7.7K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.7K
Cancers Originate from Somatic Mutations in a Single Cell
12.0K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
12.0K
The Retinoblastoma Gene
4.1K
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.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.1K
Cancer-Critical Genes I: Proto-oncogenes
9.0K
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...
9.0K
Combination Therapies and Personalized Medicine
4.9K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K
Abnormal Proliferation
4.6K
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...
4.6K


