The JDP2 Knockout NCI-H1975 Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal knockout cell population with targeted disruption of the JDP2 gene in the NCI-H1975 human non-small cell lung adenocarcinoma cell line. This genome-edited pool yields a heterogeneous loss-of-function model suitable for functional studies without requiring clonal selection, enabling robust interrogation of JDP2-dependent regulatory networks.
Derived from a lung adenocarcinoma patient, the NCI-H1975 host cell line harbors activating EGFR L858R and T790M mutations, which confer sensitivity to first- and third-generation EGFR tyrosine kinase inhibitors. This genetic background establishes NCI-H1975 as a widely used model for investigating mechanisms of acquired resistance to EGFR-targeted therapies in non-small cell lung cancer, particularly in the context of oncogenic signaling crosstalk.
JDP2 (Jun dimerization protein 2) is a basic leucine zipper transcription factor that acts as a repressor of AP-1-mediated gene expression. It dimerizes with c-Jun or ATF2 to compete with AP-1 complexes for binding to TPA-response elements (TREs), thereby suppressing transcription of downstream targets such as CDKN1A (p21), CCND1 (cyclin D1), matrix metalloproteinases, and BCL2 family members. JDP2 activity is regulated upstream by JNK and p38 MAPK phosphorylation, and it interacts with co-regulators including p300/CBP acetyltransferases, HDACs, and the SUMO-conjugating enzyme Ubc9. Through these interactions, JDP2 integrates stress and mitogenic signals to control cell cycle progression, apoptosis, and cellular differentiation.
In EGFR-mutant lung adenocarcinoma, JDP2 functions at the intersection of MAPK?CAP-1 signaling and EGFR-driven oncogenic pathways. Disruption of JDP2 in NCI-H1975 cells allows dissection of its role in modulating proliferation, survival, and therapeutic sensitivity. The knockout model facilitates exploration of how JDP2 loss alters AP-1 transcriptional output and influences responses to EGFR inhibitors such as gefitinib and osimertinib, potentially uncovering adaptive resistance mechanisms in NSCLC.
This polyclonal knockout pool supports diverse functional assays to characterize JDP2 biology. Researchers can confirm target ablation and monitor downstream effectors by western blotting and RT-qPCR, assess cell viability and proliferation via MTT and colony formation assays, and measure apoptosis using Annexin V staining. Migration and invasion assays, along with drug sensitivity testing against EGFR TKIs, enable evaluation of metastatic and resistance phenotypes. Additionally, ChIP-qPCR for TRE elements can map changes in AP-1 binding dynamics. For further details or customization, please contact Ascent Research.
