The DNASE2 Knockout AGS Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal knockout cell population in which the DNASE2 gene has been disrupted within the AGS human gastric adenocarcinoma cell line. This polyclonal population serves as a robust loss-of-function model for investigating DNASE2-mediated functions in cancer biology and innate immune signaling. The use of CRISPR/Cas9 technology ensures stable gene disruption across the cell population, enabling reproducible functional studies without the need for single-cell cloning. This model is suitable for researchers seeking to interrogate the molecular consequences of DNASE2 deficiency in a well-characterized epithelial cancer cell background.
AGS cells are a widely employed human gastric adenocarcinoma cell line that serves as a standard model for gastric cancer biology and epithelial cell signaling. Derived from a primary adenocarcinoma, these adherent epithelial cells retain key signaling pathways relevant to gastric tumorigenesis and are commonly used in drug discovery, signal transduction analyses, and cancer cell biology research. Their robust growth characteristics and well-characterized response to apoptotic stimuli make AGS cells an ideal host for studying the interplay between cell death pathways and lysosomal functions mediated by DNASE2.
DNASE2 encodes a lysosomal endonuclease that is primarily responsible for degrading DNA from apoptotic cells and during phagocytic clearance. The enzyme is regulated by transcription factors p53 and TFEB, and its expression is induced by the pro-inflammatory cytokine TNF-alpha. DNASE2 functions downstream of the apoptotic cascade, which involves p53-mediated activation of BAX and BAK, leading to mitochondrial cytochrome c release and caspase activation. The endonuclease then processes DNA fragments within lysosomes, preventing their accumulation. In the absence of DNASE2, undigested DNA fragments escape lysosomal degradation and act as damage-associated molecular patterns that activate the cGAS-STING pathway and the AIM2 inflammasome, thereby triggering potent innate immune responses and chronic inflammation.
In the AGS gastric adenocarcinoma background, DNASE2 knockout creates a unique model to explore the intersection between defective DNA degradation and tumor cell biology. Given the role of chronic inflammation in gastric cancer progression, the accumulation of DNA fragments in DNASE2-deficient AGS cells may provide insights into how impaired lysosomal function contributes to autoimmune phenomena and tumor microenvironment modulation. This model is particularly relevant for studying the activation of innate immune sensors within epithelial cancer cells and for assessing how cancer cells manage endogenous nucleic acid stress, offering a platform to investigate mechanisms linking lysosomal digestion defects to gastric cancer cell signaling and survival.
This polyclonal knockout cell population is suited for a range of experimental applications, including the analysis of apoptosis pathways via TUNEL and DNA fragmentation assays, assessment of lysosomal activity, and quantitative expression profiling using western blotting and RT-qPCR. It can be employed in flow cytometry-based cell death studies, co-immunoprecipitation experiments to probe DNASE2 interactions, and phospho-signaling investigations of downstream pathways. Furthermore, the model supports drug sensitivity screening for compounds targeting lysosomal storage disorders or autoimmune syndromes, and it aids in dissecting the cGAS-STING and AIM2 inflammasome signaling axes. For further information or inquiries, please contact Ascent Research.
