在前列腺癌中,Cyclin D-CDK4/6-INK4-RB通路的遗传改变
Monika Kmeťová Sivoňová1, Márk Híveš1, Ján Kliment2
1Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.
Molecular biology reports
|April 30, 2025
概括
细胞循环调节者的遗传变异,如环林D1,与前列腺癌风险有关. 在瘤组织中观察到CCND1,p15INK4b和RB基因的改变表达,这表明它们在前列腺癌发展中的作用.
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:
- 细胞循环失调是癌症的一个标志.
- 细胞循环的关键调节者包括循环素依赖激酶 (CDK),循环素,CDK抑制剂和视网膜母细胞瘤蛋白 (RB).
- 这些调节者的多态性和改变基因表达可能会影响癌症的易感性和进展.
研究的目的:
- 调查CDK4,CDK6,CCND1,p16INK4a,p15INK4b和RB基因中的多态化与前列腺癌风险之间的关联.
- 检查前列腺瘤组织中这些基因的mRNA表达水平,与良性前列腺增生 (BPH) 组织相比.
- 为了将基因表达与临床参数如PSA水平和病理T阶段相关联.
主要方法:
- 在CDK4,CDK6,CCND1,p16INK4a,p15INK4b和RB中使用TaqMan® SNP Assays进行特定单核酸多态 (SNP) 的基因型定型.
- 定量实时PCR (qRT-PCR) 用于测量瘤和BPH组织中研究基因的mRNA表达水平.
- 统计分析以评估多态性,基因表达和前列腺癌风险,PSA水平和T阶段之间的关联.
主要成果:
- CCND1 rs9344多态 (GA基因型) 与前列腺癌的风险增加有显著关联.
- 在前列腺瘤组织中,CCND1,p15INK4b和RB的相对mRNA表达明显低于BPH组织.
- 较低的CDK4和p16INK4amRNA表达与高的PSA水平相关,而减少的p15INK4b表达与较高的病理T阶段有关.
结论:
- 遗传变异,包括多态性和在环素D1-CDK4-p16INK4a/p15INK4b-RB通路内的改变基因表达,与前列腺癌风险有关.
- CCND1基因及其通路成员显示出潜在的前列腺癌风险和进展的生物标志物.
相关概念视频
02:34Inhibition of Cdk Activity
4.5K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.5K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
7.2K
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...
7.2K
01:20The Retinoblastoma Gene
4.0K
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,...
4.0K
02:15M-Cdk Drives Transition Into Mitosis
5.4K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.4K
02:39Positive Regulator Molecules
5.2K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.2K
03:03mTOR Signaling and Cancer Progression
3.6K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.6K