The BMAL1 Knockout AGS Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population generated through targeted disruption of the BMAL1 gene in the AGS human gastric adenocarcinoma cell line. This heterogeneous pool of cells carries various loss-of-function mutations at the BMAL1 locus, enabling functional studies without clonal selection biases. The polyclonal format retains genetic variability, making it suitable for pooled screening, bulk assays, and experiments where population-level responses to circadian or metabolic perturbations are assessed.
AGS cells are epithelial cells derived from a human gastric adenocarcinoma and serve as a model for gastric mucosal biology and gastric cancer. They retain key signaling pathways of gastric epithelium and are widely used to study Helicobacter pylori infection, oncogenic transformation, and the impact of microenvironmental factors on tumor progression. Their adherent growth and stable karyotype make them amenable to genetic manipulation and downstream assays.
BMAL1 is a core circadian transcription factor that heterodimerizes with CLOCK to bind E-box elements, driving rhythmic expression of clock genes (PER1, PER2, CRY1, CRY2) and metabolic targets (DBP, REV-ERB??, ROR??). BMAL1 activity is tightly regulated: it is deacetylated by SIRT1, phosphorylated by AMPK, and inhibited through PER/CRY negative feedback. It also integrates cues from light, feeding, and glucocorticoids. Beyond the canonical clock, BMAL1 interacts with HIF1?? under hypoxia, participates in mTOR and AMPK signaling, and influences p53-mediated cell cycle arrest, linking circadian rhythms to cancer cell metabolism and proliferation.
In gastric cancer, BMAL1 dysregulation is implicated in altered cell cycle timing, metabolic reprogramming, and tumor aggressiveness. The AGS cell line, with its gastric origin and wild-type p53, provides a relevant context for dissecting BMAL1??s roles. Knockout of BMAL1 in these cells may disrupt downstream effectors like WEE1, p21, and VEGF, shift metabolic fluxes through AMPK and insulin pathways, and impair hypoxia adaptation. Thus, this model allows systematic investigation of circadian disruption as a driver of gastric cancer phenotypes, including proliferation, apoptosis, and migration.
Researchers can utilize these polyclonal BMAL1 knockout AGS cells for diverse applications: circadian rhythm studies via luciferase reporters; gene expression analysis by RT-qPCR and RNA-seq; protein interaction studies using co-immunoprecipitation and Western blotting of CLOCK, PER, and SIRT1; chromatin occupancy assays by ChIP-qPCR; cell cycle and apoptosis analysis via flow cytometry; and functional assessments including migration/invasion and Seahorse metabolic profiling. These cells are also valuable for chronotherapy, metabolic disease modeling, and drug target validation. For further information, please contact Ascent Research.
