KDM4B Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human lung adenocarcinoma NCI-H1975 cell line. This product provides a genetically disrupted KDM4B gene model, enabling loss-of-function studies of the histone demethylase in a non-small cell lung cancer (NSCLC) background. The polyclonal format reflects a heterogeneous pool of edited cells, preserving diverse mutational outcomes and facilitating robust population-level analyses. Researchers can use these polyclonal knockout cells to interrogate KDM4B-dependent phenotypes without clonal selection artifacts, and they are suited for assays requiring sufficient cell numbers for biochemical and functional readouts.
The host NCI-H1975 cell line is a widely used human lung adenocarcinoma epithelial model originally derived from a female patient. It harbors the EGFR T790M mutation, conferring sensitivity to second- and third-generation EGFR tyrosine kinase inhibitors (TKIs) while exhibiting resistance to first-generation inhibitors. As a well-characterized model for acquired drug resistance and NSCLC biology, NCI-H1975 cells provide a clinically relevant platform to investigate epigenetic contributions to EGFR-TKI responses and tumor progression.
KDM4B is a JmjC domain-containing histone demethylase that specifically removes di- and trimethyl marks from histone H3 lysine 9 (H3K9me2/me3) and lysine 36 (H3K36me2/me3), thereby reversing transcriptional repression. Its activity is regulated by upstream signals including HIF1A, androgen receptor, TGF??, and DNA damage, and it interacts directly with factors such as the NuRD complex component MTA2, HP1?? (CBX5), and KU70 (XRCC6). By demethylating H3K9me3 at gene promoters, KDM4B promotes transcription of downstream targets like CCND1, BCL2, VEGF, BRCA1, and CHK1, thereby modulating cell cycle progression, apoptosis resistance, and DNA repair. This positions KDM4B at the nexus of oncogenic signaling, chromatin remodeling, and genomic maintenance pathways.
In the NCI-H1975 context, KDM4B likely contributes to tumorigenesis by sustaining proliferative and survival signals and by maintaining DNA repair capacity, which may influence cellular responses to EGFR inhibitors. The knockout population enables dissection of how KDM4B-mediated epigenetic regulation interfaces with EGFR-TKI sensitivity and the emergence of resistance. Additionally, its involvement in homologous recombination repair and HIF1A signaling makes this model relevant for studying hypoxia-driven adaptation and genomic instability in lung adenocarcinoma.
This polyclonal knockout cell population is applicable to numerous experimental workflows. It can be used to investigate KDM4B function in NSCLC, probe epigenetic mechanisms of EGFR TKI resistance, and analyze DNA repair and genomic stability. Typical assays include western blotting and RT-qPCR for KDM4B expression, immunofluorescence and ChIP-qPCR for H3K9me3 levels, cell proliferation (MTT) and colony formation assays, drug sensitivity profiling with EGFR inhibitors, comet assays and ??-H2AX foci formation for DNA damage assessment, and transcriptome-wide RNA-seq. For further details, contact Ascent Research.
