The BMAL1 Knockout A2780 Polyclonal Cells product consists of a population of A2780 human ovarian carcinoma cells that have undergone CRISPR/Cas9-mediated disruption of the BMAL1 (ARNTL) gene. This polyclonal knockout pool, rather than a clonally derived cell line, provides a heterogeneous loss-of-function model suitable for studying the impact of BMAL1 ablation on circadian biology and cancer cell phenotypes. The use of a polyclonal population mitigates clonal selection artifacts and maintains genetic diversity, enabling robust functional analysis of gene disruption effects across a broad cellular background.
The A2780 host cell line was originally established from an untreated patient with ovarian adenocarcinoma. It displays an epithelial morphology and is widely utilized in ovarian cancer research, particularly for investigations into platinum-based chemotherapy sensitivity and resistance mechanisms. A2780 cells are known to be sensitive to cisplatin and other DNA-damaging agents, making them a valuable platform for studying drug response in conjunction with genetic perturbations. Their well-characterized growth kinetics and genetic profile support reproducible experimentation in drug screening and circadian rhythm studies.
BMAL1 encodes a core basic helix-loop-helix-PAS transcription factor that serves as the master regulator of the mammalian circadian clock. Upon heterodimerization with CLOCK or NPAS2, BMAL1 binds to E-box enhancer elements in the promoters of target genes, driving rhythmic transcription of period (PER1, PER2) and cryptochrome (CRY1, CRY2) genes as well as clock-controlled output genes. This transcriptional oscillator is modulated by upstream regulators such as REV-ERB??, ROR??, SIRT1, and AMPK, and it directly influences the expression of downstream effectors including DBP, PPAR??, metabolic enzymes (PCK1, G6PC), and cell cycle regulators (Wee1, p21). Through these interactions, BMAL1 coordinates circadian control over cell division, metabolism, and apoptosis.
In the A2780 context, BMAL1 knockout has particular significance for ovarian cancer biology. Circadian disruption has been implicated in cancer progression, chemosensitivity, and metabolic reprogramming. Loss of BMAL1 function in this model can be exploited to dissect the molecular links between the circadian clock and pathways relevant to ovarian cancer, such as mTOR signaling, DNA damage response, and oxidative stress. This model enables researchers to investigate whether BMAL1 loss alters cisplatin sensitivity, cell proliferation rates, or metabolic flux, thereby providing insights into circadian-based therapeutic strategies.
Suggested applications include circadian bioluminescence reporter assays (e.g., PER2::LUC) to monitor clock disruption, RT-qPCR profiling of clock gene expression, and Western blot analysis of downstream proteins. Cell-based assays such as MTT/BrdU proliferation, flow cytometric cell cycle analysis, and Annexin V apoptosis detection can assess functional consequences of BMAL1 knockout. Additionally, cisplatin sensitivity testing and Seahorse metabolic flux analysis allow exploration of drug resistance and metabolic rewiring. Chromatin immunoprecipitation (ChIP-qPCR) can map BMAL1 binding sites, and compound screening for clock modulators is facilitated by this model. For further information, please contact Ascent Research.
