How Stable Reporter Cell Lines Advance Therapeutic Target Discovery and Compound Screening

Cell culture models as a cornerstone of biological research

Biological processes are regulated on multiple levels, and experimental models should reflect this complexity. However, model systems should also ensure reproducibility, standardized experimental conditions, and reasonable timelines in order to streamline research. Cell-based models provide a platform to evaluate biological processes in a straight-forward and reproducible manner, even though they cannot recapitulate the full complexity of living organisms. Thus, cell cultures have been established as key models to elucidate gene and cell functions. Moreover, cell-based models have proven to be indispensable for therapeutic target identification and high-throughput drug candidate screening.1 

Primary cells and immortalized cell lines in biological research

Both primary cells and immortalized cell lines have been widely used in life science research and have advantages and limitations. Primary cells are isolated from living organisms and can be expected to reflect the investigated biological processes more closely. However, immortalized cell lines are also associated with important advantages, such as cost effectiveness, ease of use, homogeneity of the cellular population, and no need to obtain informed consent.2 

Cell-based models as tools for pharmacological and toxicological research

Cell-based models, including both primary cells and cell lines, have found extensive applications in the fields of drug screening and toxicology as they provide the opportunity for efficient, high-throughput analysis. The use of cell-based models has been instrumental for the identification of numerous drug candidates that have subsequently progressed to evaluation in in vivo models. However, due to the high rate of failure of drug candidates during later stages of the drug development process, there are consistent efforts to establish optimized cell-based models.3

The role of molecular biological techniques in cell-based experimental models

Molecular biological manipulations can regulate the expression of genes through their overexpression or knockdown. Thus, molecular biological techniques can play an important role in the elucidation of gene functions and of gene effects on downstream signaling molecules. Moreover, transfection of reporter vectors can be used to gain insight into the function of cellular signaling pathways. Frequently, transient transfections are performed. However, they result in gene expression changes with limited duration, leading to a burdensome and time-consuming experimentation process. 

Stable reporter cell lines and their role for elucidating the molecular underpinnings of cell functions

Stable reporter cell lines offer a solution for several of the challenges posed by transient transfections. The establishment of stable reporter cell lines includes the integration of reporter expression cassettes into the genomes of cells using lentivirus or plasmid vectors. Thus, permanent gene integration is achieved, and no repeated transfections are needed. However, the development of stable reporter cell lines is time-consuming, associated with high costs, and requires extensive expertise in the fields of cellular and molecular biology. Signosis has established a wide range of luciferase and gene expression stable reporter cell lines that enable researchers to use these valuable resources and focus on their scientific questions without wasting time and financial resources on stable cell line development.

Luciferase Reporter Stable Cell Lines Luciferase reporter cell assays have been established as valuable tools to identify ligands for cell signaling pathways and transcription factors as well as to screen for receptor agonists and antagonists.4 Signosis has developed and validated a range of sensitive, responsive, reliable, and easy-to-use luciferase reporter cell lines. They enable the analysis of transcription factor activity, thus gaining insight into the function of downstream signaling pathways. 

Gene Expression Stable Cell Lines Our team of talented and experienced scientists have created cell lines stably expressing genes that are key for the regulation of cellular functions, including among many others GSK-3β, P53, NF-κB, and MMP-9. One of the areas we have specifically focused on is the development of stably expressing cell lines relevant for different aspects of tumor biology, such as EGFR and HER2 (ERBB2) Stably

Expressing Cell Lines. 

In addition, we have established other stably expressing reporter cell systems, such as GAL4 Reporter Stable Cell Lines that are highly sensitive and specific models for the analysis of gene expression and function or Bioluminescent tumor cell lines that play an important role in cancer research and especially in the imaging of xenograft tumors.

Stable reporter cell lines as valuable tools to elucidate cell functions

Cell-based models are indispensable tools for biological research. Moreover, molecular biological manipulations can provide insight into the molecular mechanisms underlying cellular functions. In particular, stable reporter cell lines enable researchers to analyze gene and cell functions without the inconvenience of repeated transfections. Signosis has developed a wide range of highly sensitive, responsive, and consistent stable reporter cell lines that can facilitate and streamline research. 

Resources

1. Vertrees RA, Jordan JM, Solley T, Goodwin TJ. Tissue culture models. Basic Concepts of Molecular Pathology. 2009;2:159–82. doi: 10.1007/978-0-387-89626-7_18. 

2. Kaur G, Dufour JM. Cell lines: Valuable tools or useless artifacts. Spermatogenesis. 2012;2(1):1-5. doi: 10.4161/spmg.19885.

3. Astashkina A, Mann B, Grainger DW. A critical evaluation of in vitro cell culture models for high-throughput drug screening and toxicity. Pharmacol Ther. 2012;134(1):82-106. doi: 10.1016/j.pharmthera.2012.01.001.

4. Lai C, Jiang X, Li X. Development of luciferase reporter-based cell assays. Assay Drug Dev Technol. 2006;4(3):307-15. doi: 10.1089/adt.2006.4.307.How stable reporter cell lines advance therapeutic target discovery and compound screening