The KDM5B Knockout NCI-H1299 Polyclonal Cells provide a CRISPR/Cas9-edited polyclonal knockout population in NCI-H1299 human lung adenocarcinoma cells, enabling functional loss of KDM5B. This gene-edited product introduces a disruption at the endogenous locus, eliminating KDM5B protein expression. The polyclonal format preserves cell population diversity, supporting robust and reproducible investigation of KDM5B-dependent phenotypes without clonal artifacts.
The parental NCI-H1299 line, derived from a lymph node metastasis of a lung adenocarcinoma in a 43-year-old male, is a well-characterized model of non-small cell lung carcinoma with high metastatic propensity. These cells display an epithelial-to-mesenchymal transition phenotype and harbor a p53 null mutation, which abrogates normal growth control. Consequently, NCI-H1299 cells rely heavily on epigenetic mechanisms, making them particularly valuable for dissecting KDM5B-mediated gene regulation.
KDM5B (JARID1B/PLU-1) is a JmjC-domain histone H3K4 demethylase that removes tri- and di-methylation marks, functioning as a transcriptional repressor of genes involved in cell cycle arrest and apoptosis. It is activated by upstream signals including MYC, HIF-1??, and the Notch intracellular domain, and it assembles into repressor complexes with HDAC1/2, EZH2 (PRC2), SIN3A, the NuRD remodeling complex, and the SWI/SNF subunit ARID1A. Key downstream targets silenced by KDM5B include the CDK inhibitors CDKN1A (p21) and CDKN2B (p15), along with HOX gene clusters and E-cadherin. Representative regulatory cascades such as MYC??KDM5B??H3K4me3 demethylation??CDKN1A repression and HIF-1????KDM5B??metabolic gene silencing underscore its central role in proliferation, epigenetic plasticity, and stem cell maintenance.
Within NCI-H1299 cells, KDM5B is believed to maintain aggressive tumor behavior by sustaining a repressive chromatin environment at tumor suppressor loci. Its genetic disruption is predicted to reactivate CDKN1A and CDKN2B, restore cell cycle checkpoints, and impair invasive capacity, while also modulating sensitivity to chemotherapy. The polyclonal configuration of these knockout cells allows for examination of heterogeneous responses and the identification of compensatory pathways that may arise upon loss of KDM5B function.
This product is intended for advanced biomedical studies, including epigenetic regulation in NSCLC, validation of KDM5B as a therapeutic target, and exploration of cancer stem cell dynamics. Experimental approaches well-suited to this model include MTT or BrdU proliferation assays, Transwell migration/invasion assays, clonogenic assays, ChIP-qPCR for H3K4me3 occupancy, RT-qPCR for target gene analysis, western blotting for KDM5B and downstream effectors, and drug sensitivity screens. For additional support, please contact Ascent Research.
