孕激素受体-Grb2相互作用与乳腺癌的更好的结果有关
Nattamolphan Wittayavimol1, Erina Iwabuchi2, Prangwan Pateetin1
1Department of Clinical Chemistry and Graduate Program in Clinical Biochemistry and Molecular Medicine, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
The Journal of steroid biochemistry and molecular biology
|December 9, 2023
概括
孕激素受体 (PR) 与Grb2相互作用,抑制EGF信号传递并减少乳腺癌细胞的增殖. 这种PR-Grb2相互作用与更好的乳腺癌预后相关.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 癌症研究 癌症研究
背景情况:
- 孕激素受体 (PR) 具有通过其聚烯域 (PPD) 介导的核外功能,与细胞质SH3域相互作用.
- PR-PPD-SH3相互作用抑制了EGF介导的信号传递,并降低了肺癌细胞的增殖.
- Grb2是一种具有SH2和SH3域的适配蛋白,对信号传导至关重要.
研究的目的:
- 研究PR和Grb2在乳腺癌细胞和组织中的相互作用.
- 为了确定PR-PPD是否与Grb2-SH3域相互作用.
- 评估PR-Grb2相互作用在乳腺癌预后中的临床意义.
主要方法:
- GST-pulldown测试证实了PR-PPD和Grb2-SH3的相互作用.
- 免疫光染色以可视化乳腺癌细胞中PR和Grb2的同位化.
- 双分子光补充 (BiFC) 和近距离结合试验 (PLA) 来检测细胞和患者组织中的PR-Grb2相互作用.
主要成果:
- 特别是PR-PPD与Grb2.2的SH3域相互作用.
- PR和Grb2在乳腺癌细胞的核和细胞质中同位.
- PR-Grb2相互作用与较低的组织学阶段和减少的淋巴结转移有关.
结论:
- 与Grb2的PR-PPD相互作用对于抑制EGF介导的信号传输至关重要.
- PR-Grb2相互作用与PR-和Grb2-阳性乳腺癌的更好的预后有关.
- 这种相互作用为新型癌症疗法提供了潜在的目标.
相关概念视频
TGF - β Signaling Pathway
7.4K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K
GPCR Desensitization
6.1K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
6.1K
Mitogens and the Cell Cycle
6.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K
GPCRs Regulate Adenylyl Cylase Activity
5.6K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.6K
G Protein-coupled Receptors
12.1K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
12.1K
G-protein Coupled Receptors
119.5K
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
119.5K


