功能分析揭示了驱动器合作性和子宫内膜癌发生的新机制
Matthew Brown1,2, Alicia Leon3, Katarzyna Kedzierska1
1Cancer Genomics and Immunology Group, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
EMBO molecular medicine
|August 17, 2023
概括
基因工程小鼠模型显示FBXW7,PTEN和TP53突变驱动高风险子宫内膜癌. 针对LEF1信号可能为这种侵袭性疾病提供新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 高风险的子宫内膜癌具有显著的临床挑战,其发病率不断增加,预后不佳.
- 高风险子宫内膜癌的分子驱动因素仍然不完全理解,阻碍了治疗的发展.
研究的目的:
- 用基因工程小鼠模型阐明FBXW7,PTEN和TP53突变在子宫内膜癌发生过程中的功能后果.
- 确定高风险子宫内膜癌的新型分子通路和潜在的治疗点.
主要方法:
- 利用基因工程小鼠模型 (GEMM) 研究Fbxw7,Pten和Tp53突变的综合影响.
- 在小鼠和人类子宫内膜癌样本和细胞系上进行了转录基因分析.
- 使用分子生物学技术验证了新的FBXW7基质.
主要成果:
- 确定TP53误解突变是比TP53删除更强大的子宫内膜癌发生的驱动因素.
- 单独FBXW7误解突变并没有诱导瘤,但显著加速了由PTEN损失或TP53误解突变驱动的致癌.
- 在FBXW7突变子宫内膜癌中,LEF1信号被发现是上调的,LEF1和TCF7L2被验证为新的FBXW7基质.
结论:
- FBXW7,PTEN和TP53突变在高风险子宫内膜癌的发病过程中发挥着关键作用.
- 对于耐治疗子宫内膜癌子组来说,LEF1信号代表了一个潜在的治疗标.
相关概念视频
Cooperative Binding of Transcription Regulators
6.5K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
6.5K
Hormonal Control of the Ovarian Cycle
568
The ovarian cycle is meticulously regulated by the hypothalamic-pituitary-gonadal axis. This cycle orchestrates the release of a mature oocyte, essential for reproduction.
Before puberty, the hypothalamus releases GnRH in a low frequency, low amplitude pulsatile manner. This along with the immature hypothalamic-pituitary-gonadal axis activity, results in low estrogen levels and the absence of a fully functional ovarian cycle. At puberty, GnRH secretion increases in both frequency and...
Before puberty, the hypothalamus releases GnRH in a low frequency, low amplitude pulsatile manner. This along with the immature hypothalamic-pituitary-gonadal axis activity, results in low estrogen levels and the absence of a fully functional ovarian cycle. At puberty, GnRH secretion increases in both frequency and...
568
Adaptive Mechanisms in Cancer Cells
5.8K
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,...
5.8K
Oogenesis
63.8K
In human women, oogenesis produces one mature egg cell or ovum for every precursor cell that enters meiosis. This process differs in two unique ways from the equivalent procedure of spermatogenesis in males. First, meiotic divisions during oogenesis are asymmetric, meaning that a large oocyte (containing most of the cytoplasm) and minor polar body are produced as a result of meiosis I, and again following meiosis II. Since only oocytes will go on to form embryos if fertilized, this unequal...
63.8K
Cooperative Allosteric Transitions
7.9K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
7.9K
Mechanisms of Retrovirus-induced Cancers
5.1K
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
5.1K


