急性或慢性酸性和缺氧对瘤细胞基因表达模式的影响:潜在的功能影响
O Thews1, S Reime2, V Dubourg2
1Julius-Bernstein-Institute of Physiology, University of Halle, Halle, Germany. oliver.thews@medizin.uni-halle.de.
Advances in experimental medicine and biology
|October 14, 2024
概括
暴露于短期或长期酸化的瘤细胞显示基因表达的改变. 慢性酸性诱导明显的变化,表明瘤细胞适应低pH环境.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 瘤经常经历缺氧和细胞外化症,这是由于糖分分解的增加.
- 瘤内的代谢变化可以显著影响基因表达模式.
研究的目的:
- 在急性 (24小时) 和慢性 (5周) 酸化下,研究瘤细胞的基因表达变化.
- 为了比较酸化和缺氧对不同癌症细胞系基因表达的影响.
主要方法:
- 三种癌细胞系 (AT1,MCF-7,MDA-MB-231) 接受了24小时的酸性化 (pH6.6) 和缺氧 (pO2 1.5 mmHg).
- 在酸性条件下 (pH 6.6) 长期培养AT1细胞 (5周).
- 用总RNA测序分析基因表达,并通过基因本体学丰富进行功能分析.
主要成果:
- 急性酸化 (24小时) 在AT1和MCF-7细胞中显著改变基因表达,但在MDA-MB-231细胞中最小.
- 缺氧对MCF-7细胞的影响最大.
- 短期的酸性会对RNA处理,细胞循环调节,DNA合成和线粒体功能产生负面影响.
- 在AT1细胞中,慢性酸性酶导致1160个基因的差异表达,影响组织发育,RNA处理和线粒体活动.
结论:
- 急性和慢性酸性都会改变瘤细胞的基因表达和功能.
- 长期的酸性酶诱导基因表达的变化从根本上有所不同,这表明瘤细胞适应低pH的过程.
相关概念视频
02:53Adaptive Mechanisms in Cancer Cells
5.7K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.7K
02:49Cancer Therapies
7.6K
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
7.6K
01:37Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
01:24Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
01:58Cell Specific Gene Expression
13.5K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.5K
01:23Hypoxia
960
Hypoxia is a medical condition characterized by an inadequate oxygen supply to body tissues. It typically manifests as a bluish discoloration of the skin and mucosae, especially in fair-skinned individuals, when hemoglobin (Hb) saturation drops below 75%.
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
960