The EIF2AK2 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the NCI-H1975 non-small cell lung cancer (NSCLC) line. This product disrupts the EIF2AK2 gene encoding PKR, providing a heterogeneous loss-of-function model without clonal selection.
The NCI-H1975 cell line originates from a female never-smoker with lung adenocarcinoma and carries EGFR L858R/T790M and PIK3CA mutations. These genetic lesions drive constitutive EGFR and PI3K/AKT signaling, making the line a standard model for studying EGFR tyrosine kinase inhibitor resistance and oncogenic signaling.
EIF2AK2 encodes PKR, an interferon-inducible kinase activated by dsRNA, interferons (IFN-??/??/??), TNF-??, oxidative stress, and Toll-like receptors (TLR3/4) via the cofactor PACT. Upon activation, PKR phosphorylates eIF2??, inhibiting translation and triggering stress granule assembly. It also activates NF-??B through the IKK complex, stabilizes p53, and modulates JNK signaling. PKR interacts with molecular partners such as TRBP, RIPK1, TRAF proteins, and Hsp90. Through these interactions, PKR integrates pathogen-sensing and stress signals to regulate apoptosis, inflammation, and antiviral responses.
In NCI-H1975 cells, PKR intersects with EGFR and PI3K/AKT pathways, influencing sensitivity to EGFR-TKIs and cell fate decisions. Loss of PKR in this polyclonal model enables dissection of its role in modulating eIF2?? phosphorylation, ATF4/CHOP induction, NF-??B/p53 activity, and apoptotic outcomes under drug treatment or viral mimicry, without clonal bias.
Applications include antiviral innate immunity studies using poly(I:C) or viral challenge, integrated stress response analysis, and EGFR-TKI resistance profiling. Compatible assays include Western blotting (EIF2AK2, phospho-eIF2??, NF-??B, p53), RT-qPCR (IFN-??, CHOP, ATF4), immunofluorescence (stress granules), drug sensitivity testing (osimertinib), apoptosis assays, NF-??B reporter assays, and RNA-seq. For inquiries, contact Ascent Research.
