The IKZF5 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1975 human lung adenocarcinoma cell line. This product comprises a heterogeneous pool of cells with targeted disruption of the IKZF5 gene, achieved via CRISPR/Cas9-mediated gene editing. As a polyclonal knockout model, it captures diverse editing outcomes without clonal selection, providing a physiologically relevant loss-of-function system for studying IKZF5-dependent processes in NSCLC.
NCI-H1975 is an epithelial cell line originating from a non-small cell lung cancer patient, harboring the activating EGFR L858R mutation and the T790M gatekeeper mutation. These genetic lesions render the cells dependent on EGFR signaling while also contributing to acquired resistance against first-generation tyrosine kinase inhibitors. Widely used as a model for EGFR-mutant lung adenocarcinoma, NCI-H1975 facilitates investigation of oncogenic signaling and therapeutic resistance mechanisms.
IKZF5 encodes a zinc-finger transcription factor that represses gene expression by recruiting corepressor complexes such as HDACs and CtBP to specific DNA sites. Within the Notch pathway, IKZF5 is transcriptionally regulated by CSL/RBPJ and functions alongside targets like HES1. It directly suppresses genes critical for cell cycle arrest and apoptosis, notably CDKN1A (p21) and BCL2L1. Post-translational modifications by casein kinase II and protein kinase A modulate its activity, linking extracellular cues to transcriptional outputs.
In EGFR-mutant NCI-H1975 cells, IKZF5 disruption offers a means to examine the non-hematopoietic roles of Ikaros family proteins. Loss of IKZF5 may alter transcriptional networks that intersect with EGFR-driven proliferation and survival, potentially affecting drug sensitivity. The polyclonal knockout format avoids clonal bias, making it suited for studying heterogeneous responses to targeted therapies and identifying novel drug-resistance pathways.
This knockout product enables functional genomics screening for EGFR inhibitor resistance modifiers, mechanistic dissection of IKZF5-mediated regulation via ChIP-qPCR and RNA-seq, and molecular validation through Western blotting and RT-qPCR. Cell-based assays for proliferation, apoptosis, and drug sensitivity with agents such as gefitinib or osimertinib can further probe IKZF5??s role in treatment responses. For additional information or to request a quote, please contact Ascent Research.
