The JUND Knockout NCI-H1975 Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal population in which the JUND gene has been disrupted. Derived from the human NCI-H1975 lung adenocarcinoma cell line, these polyclonal knockout cells enable loss-of-function studies of JUND without clonal selection artifacts. They are delivered as a ready-to-use edited cell pool suitable for diverse molecular and cellular assays.
NCI-H1975 is a non-small cell lung cancer line derived from a female nonsmoker with adenocarcinoma. It harbors activating EGFR mutations (L858R and T790M) and a TP53 mutation, representing a clinically relevant model for EGFR-targeted therapy and acquired resistance. The oncogenic EGFR signaling drives proliferation and survival, making it an ideal host for investigating AP-1 transcription factor functions in lung cancer.
JUND encodes an AP-1 transcription factor subunit. Activated downstream of EGFR, the RAS-RAF-MEK-ERK cascade stimulates ERK1/2 and JNK, which phosphorylate c-Jun and ATFs, promoting dimerization with JUND to form active AP-1 complexes. JUND regulates genes such as Cyclin D1 and MMP-9, mediating proliferation and invasion. It interacts with c-Jun, Fos, and ATF family members, integrating signals from growth factors and cytokines.
In NCI-H1975 cells, JUND knockout disrupts AP-1-mediated transcription in an EGFR-mutant context. This model allows researchers to explore how loss of JUND affects EGFR-dependent proliferation, apoptosis, and drug sensitivity. Given the T790M mutation conferring TKI resistance, the cells can be used to assess JUND??s role in resistance mechanisms and to identify synthetic vulnerabilities.
Applications include AP-1 functional studies via western blotting (JUND, c-Jun, pERK), RT-qPCR, RNA-seq, and ChIP-qPCR. Functional assays encompass flow cytometry for cell cycle and apoptosis, co-immunoprecipitation of AP-1 complexes, and migration/invasion analyses. Drug sensitivity testing with EGFR inhibitors can be performed. The polyclonal pool is suitable for xenograft models to evaluate tumorigenicity and therapeutic response in vivo. For technical inquiries, contact Ascent Research.
