The HMGB2 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human non-small cell lung adenocarcinoma line NCI-H1975. This product provides a genetically disrupted HMGB2 loss-of-function model, generated by CRISPR/Cas9-mediated gene disruption, and is supplied as a polyclonal pool. The heterogeneous cell population retains the tumorigenic background of the parental line while enabling studies of HMGB2 functional ablation in a physiologically relevant lung cancer context.
The NCI-H1975 cell line originates from a female patient with non-small cell lung carcinoma and harbors activating EGFR L858R and T790M mutations, which constitute a clinically relevant model of acquired resistance to first-generation tyrosine kinase inhibitors. These cells exhibit oncogenic EGFR signaling and are widely used to investigate molecular mechanisms driving lung adenocarcinoma progression, drug resistance, and metastasis. The integration of HMGB2 knockout into this background allows dissection of the gene??s role in EGFR-mutant lung cancer.
HMGB2 encodes a non-histone chromatin-associated protein that functions dually as a nuclear architectural factor and extracellular damage-associated molecular pattern (DAMP). Intranuclearly, it modulates DNA repair and transcription by facilitating chromatin remodeling and interacting with factors such as p53, histones, and HMGA1. Upon active secretion or passive release, extracellular HMGB2 binds to receptors RAGE and TLR4, activating MyD88-dependent signaling pathways that converge on NF-??B and MAPK cascades. The protein is transcriptionally regulated by SP1 and NF-??B and is induced by pro-inflammatory stimuli including TNF-??, IL-1??, and LPS. Known downstream targets of HMGB2-mediated signaling include cytokines IL-6 and TNF, chemokine CXCL8, matrix metalloproteinase MMP9, and cell cycle regulator Cyclin D1.
In NCI-H1975 cells, the EGFR L858R/T790M mutations drive persistent signaling through AKT and MAPK pathways, creating a milieu where HMGB2 may further influence tumor-promoting inflammation and invasion. Extracellular HMGB2 could amplify NF-??B activity via RAGE/TLR4 engagement, potentially enhancing expression of pro-metastatic factors like MMP9 and CXCL8. Knockout of HMGB2 in this polyclonal population enables systematic analysis of its contribution to inflammatory oncogenesis, DNA damage responses, and drug resistance mechanisms. This model is particularly suited to dissect crosstalk between oncogenic EGFR signaling and HMGB2-mediated inflammatory networks.
Researchers can employ this knockout model to investigate HMGB2-dependent regulation of gene expression, cytokine production, and signaling pathway activation using assays such as RT-qPCR for cytokine profiling, NF-??B luciferase reporter measurements, and phospho-signaling analysis of MAPK and AKT. Functional characterization of invasion and migration can be assessed via Transwell assays, while flow cytometry permits evaluation of apoptosis. The polyclonal knockout cells also serve as a screening platform for pharmacological agents targeting HMGB2-related pathways or EGFR-driven lung cancer. For further details or to request a quote, please contact Ascent Research.
