Resf1是一种化合物G4四倍体关联瘤抑制剂,用于三阴性乳腺癌
Megan R Majocha1,2, Devin E Jackson1,2, Ngoc-Han Ha1
1Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS genetics
|May 9, 2024
概括
丢失Resf1基因加速瘤生长和转移雌激素受体阴性乳腺癌,表明其作为瘤抑制剂的作用. 这一发现对于理解和潜在治疗侵袭性乳腺癌亚型至关重要.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 雌激素受体阴性 (ER-) 乳腺癌的预后不佳,转移率高.
- 转移是癌症死亡的主要原因,需要对其潜在机制进行研究.
- 之前的研究使用小鼠系统遗传学方法确定了12个与转移性易感性相关的基因.
研究的目的:
- 为了确定与ER乳腺癌转移性易感性相关的新基因.
- 为了研究差异化基因Resf1在ER-乳腺癌进展和转移中的作用.
主要方法:
- 使用CRISPR和基因陷的小鼠模型与MMTV-PyMT基因工程小鼠模型交叉.
- 评估瘤生长,整体存活率和发病率/肺转移的数量在减少Resf1.
- 分析了匹配的尾巴和主要瘤组织,以调查Resf1的潜在瘤抑制功能.
- 进行了机械分析,以探索Resf1在转录控制和G4四重复相互作用中的作用.
主要成果:
- 减少Resf1显著增加了瘤生长,并降低了MMTV-PyMT小鼠的整体存活率.
- 丢失Resf1导致更高的发病率和更多的肺转移.
- 分析显示,瘤组织中野生型Resf1拷贝的丢失,支持其作为瘤抑制剂的作用.
- 机理学研究表明Resf1参与了转录控制,特别是在核糖体生物发生路径中,通过与G4四重复合体的关联.
结论:
- 在ER-乳腺癌中,Resf1被确定为一种新型的转移易感基因.
- 在ER-乳腺癌中,Resf1功能的丧失促进了瘤的进展和转移.
- 通过调节转录和转化控制,特别是核糖体生物发生,Resf1可能起到瘤抑制作用.
相关概念视频
01:20The 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
01:23Negative Regulator Molecules
35.3K
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.
35.3K
02:38The Ras Gene
6.2K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
6.2K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
7.4K
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...
7.4K
02:23Abnormal 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
01:12Loss of Tumor Suppressor Gene Functions
4.8K
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.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.8K