The BRD2 Knouckout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the SK-HEP-1 cell line, engineered for loss-of-function studies of the BRD2 gene. This product comprises a heterogeneous pool of cells with targeted disruption at the BRD2 locus, enabling investigation of BRD2-dependent transcriptional regulation. The polyclonal format preserves genetic diversity, making it suitable for studying population-level responses and resistance mechanisms. No single-cell cloning was performed, so the population may contain cells with varied mutations at the target site.
SK-HEP-1 cells are a human liver adenocarcinoma line originally isolated from the ascites of a patient with hepatic adenocarcinoma. These cells are widely used as a model of liver cancer, exhibiting properties relevant to hepatocellular carcinoma and hepatic metastases. The SK-HEP-1 cell line displays aggressive tumorigenic features, including rapid proliferation and dysregulated signaling pathways common in liver cancer. Its hepatic origin provides a relevant platform for examining liver oncogenesis and drug responses.
BRD2 is a member of the bromodomain and extraterminal (BET) family of acetyl-histone readers. It binds acetylated lysine residues on histones H3K27 and H4K5 via tandem bromodomains, recruiting the Mediator complex and P-TEFb (CDK9/Cyclin T1) to facilitate transcriptional elongation. BRD2 predominantly regulates genes involved in cell proliferation and survival, including MYC, CCND1, BCL2, BCL2L1, and CDK6. Its activity is modulated by upstream signals such as p300/CBP acetylation, CDK9 kinase activity, and cytokines (TNF-??, IL-6) through JAK/STAT pathways. BRD2 further interacts with transcription factors like E2F, NF-??B p65, and STAT3, and cooperates with BRD3 and BRD4 to integrate growth and inflammatory signals.
In SK-HEP-1 liver adenocarcinoma cells, BRD2 knockout disrupts the BET protein-mediated transcriptional network, potentially impairing MYC-driven oncogenic programs. Given that BRD2 is upregulated in various cancers and contributes to BET inhibitor sensitivity, this model allows dissection of BRD2-specific functions distinct from BRD4. By eliminating BRD2, researchers can examine its role in sustaining liver cancer cell proliferation, apoptosis evasion, and inflammatory crosstalk. This is particularly relevant for understanding epigenetic vulnerabilities in hepatocellular carcinoma and for evaluating therapeutic strategies targeting BET proteins.
Typical applications include profiling BET protein functions via RNA-seq transcriptomics, ChIP-qPCR for H3K27ac occupancy, and co-immunoprecipitation of transcription complexes. The polyclonal knockout cells can be used to assess BRD2-dependent drug sensitivity using MTS proliferation assays and Annexin V apoptosis detection, as well as to investigate resistance mechanisms to BET inhibitors. Additional experiments may involve Western blotting and RT-qPCR to confirm BRD2 loss and its impact on downstream targets like MYC and CCND1. This tool supports liver cancer biology research, epigenetic regulation studies, and drug target validation. For further information, please contact Ascent Research.
