The GFRAL (Glial Cell Line-Derived Neurotrophic Factor Receptor Alpha-like) gene and the RET (Rearranged during Transfection) proto-oncogene are both involved in the development and maintenance of the nervous system. GFRAL is a receptor for glial cell line-derived neurotrophic factor (GDNF), which is essential for the survival and differentiation of various neuronal populations. RET, on the other hand, is a receptor tyrosine kinase that plays a role in cell growth, differentiation, and survival, and its dysregulation is associated with several neuroendocrine tumors and developmental disorders.
In the context of cell lines, the HEK293 cell line has been modified to stably express both GFRAL and RET. This engineered cell line provides a unique model to study the complex interactions between these two proteins and their downstream signaling pathways. Researchers can utilize this stable cell line to explore the molecular mechanisms underlying neurotrophic factor signaling and its implications in neuronal development and disease. Additionally, the cell line can be used to screen for compounds that modulate GFRAL/RET signaling, potentially leading to therapeutic interventions for related disorders.
Chemotherapy-treated cancer patients develop cachexia along with anorexia, body weight loss, and the loss of adipose and skeletal muscle tissue. The scientists used combinatorial antibody phage library biopanning to create A11, a completely human GFRAL antagonist antibody. Serum response element-luciferase reporter activity was significantly reduced (up to 74%) indicating that A11 effectively suppressed GDF15-induced signaling. In a melanoma mouse model, A11 treatment alleviated anorexia and body weight loss by lowering GFRAL-positive neuron populations and attenuating the effects of cisplatin-induced GDF15 on the brainstem in vivo. Furthermore, A11 lessened the cisplatin-induced depletion of skeletal muscle and adipose tissue, indicating its promise as a treatment approach for chemotherapy-induced cachexia.
Figure 1. The researchers established a GFRAL/RET Stable Cell Line - HEK293 to investigate antibody A11's impact on inhibiting GDF15/GFRAL/RET axis signaling. Experimental methods included SPR, flow cytometry, immunostaining, and Western blot analysis. (Lee BY, et al., 2023)
The Human GFRAL/RET Stable Cell Line - HEK293 is a cell line that expresses both the Gastrin-releasing peptide receptor (GFRAL) and the RET proto-oncogene. This cell line has several applications in the field of (1)cancer research:
Cancer Biology: The co-expression of GFRAL and RET provides a platform to study the interaction between these two proteins, which is crucial for understanding the development of cancers driven by RET signaling, such as medullary thyroid carcinoma.
Drug Screening: This cell line can be utilized to screen for small molecules or biologics that inhibit the GFRAL/RET signaling pathway, potentially leading to the discovery of new therapeutic agents for RET-driven cancers.
Signaling Pathway Analysis: Researchers can use this cell line to dissect the downstream signaling pathways activated by GFRAL and RET, which can help in identifying novel targets for cancer therapy.
Customer Q&As
How does the Human GFRAL/RET Stable Cell Line - HEK293 contribute to the study of the roles of GFRAL and RET receptors in tumorigenesis?
A: The Human GFRAL/RET Stable Cell Line - HEK293, by stably expressing GFRAL and RET receptors in HEK293 cells, provides an experimental platform to study the roles of these receptors in tumor development. This cell line enables scientists to simulate a tumor cell environment and investigate how the activation of GFRAL and RET receptors affects cell proliferation, differentiation, and apoptosis. This is crucial for developing targeted therapeutic strategies against these receptors.
What role does the Human GFRAL/RET Stable Cell Line - HEK293 play in the drug screening for developing RET kinase inhibitors?
A: The Human GFRAL/RET Stable Cell Line - HEK293 serves as a model for drug screening to help scientists screen and validate inhibitors targeting RET kinase. By testing compounds in these cells, researchers can evaluate their effects on RET kinase activity, leading to the discovery of potential anticancer drug candidates, which is significant for treating cancers associated with RET mutations.
What applications does the Human GFRAL/RET Stable Cell Line - HEK293 have in studying the roles of GFRAL and RET receptors in neural development?
A: The Human GFRAL/RET Stable Cell Line - HEK293 can be used to study the roles of GFRAL and RET receptors in neural development, particularly in neuronal differentiation and synapse formation. This cell line helps scientists understand how these receptors affect neural cell signaling and function, providing new perspectives for the treatment of neural development-related diseases.
What advantages does the Human GFRAL/RET Stable Cell Line - HEK293 provide in studying GFRAL and RET receptor-mediated cell signaling?
A: By stably expressing these receptors, the Human GFRAL/RET Stable Cell Line - HEK293 offers a controlled environment to study GFRAL and RET receptor-mediated cell signaling. This cell line allows researchers to analyze signaling pathways at the molecular level in detail, including receptor activation, downstream signaling molecule activation, and how these signals affect cell behavior.
How can the accuracy of experiments be ensured when using the Human GFRAL/RET Stable Cell Line - HEK293 to study the roles of GFRAL and RET receptors in apoptosis?
A: Ensuring the accuracy of experiments when studying apoptosis with the Human GFRAL/RET Stable Cell Line - HEK293 relies on standardizing experimental conditions, including cell culture, drug treatment, and apoptosis detection methods. Additionally, using control groups and replicate experiments can enhance data reliability. These methods allow researchers to more accurately assess the roles of GFRAL and RET receptors in the apoptotic process.
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High Expression Potential
The Human GFRAL/RET Stable Cell Line - HEK293 efficiently expresses GFRAL and RET genes, providing a powerful tool for studying their functions.
Biological Research Platform
This cell line serves as a versatile platform for studying signal transduction and protein interactions, widely applied in various biological experiments.
Virus Packaging Capability
The HEK293 cell line excels in virus packaging research, aiding in the development of novel viral vectors.
Disease Model Construction
The Human GFRAL/RET Stable Cell Line provides a stable cellular model for studying related diseases, advancing the elucidation of disease mechanisms.
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