The JADE1 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population providing a loss-of-function model for JADE1, a scaffold protein of the HBO1 histone acetyltransferase complex. Derived from NCI-H1975 lung adenocarcinoma cells, these polyclonal cells offer a heterogeneous gene-edited population suitable for studying JADE1-dependent processes without clonal bias. This model enables dissection of JADE1’s roles in epigenetic regulation, cell cycle control, and signaling.
The NCI-H1975 cell line, isolated from a female with metastatic lung adenocarcinoma, carries EGFR L858R and T790M mutations and serves as a widely used model for EGFR-mutant non-small cell lung carcinoma. The line was established from a pleural effusion of a non-smoking female and is extensively used to study acquired resistance to first-generation EGFR inhibitors and to screen third-generation agents. These adherent epithelial cells provide a clinically relevant background to interrogate JADE1 function in advanced lung cancer.
JADE1 is an essential scaffold of the HBO1/KAT7 acetyltransferase complex (also containing ING4/5 and MEAF6) that acetylates histone H4 at DNA replication origins, facilitating origin licensing and DNA replication. Additionally, JADE1 functions as a transcriptional co-activator: in Wnt/??-catenin signaling, it interacts with CTNNB1 downstream of WNT3A/FZD/DVL/GSK3B to regulate TCF/LEF target genes like MYC and CCND1, and in the p53 pathway, it is regulated by TP53 and controls CDKN1A expression linking DNA damage to cell cycle arrest. Thus, JADE1 integrates Wnt and p53 signals to control proliferation and genome integrity.
In NCI-H1975 cells, JADE1 knockout enables dissection of how the HBO1 complex and Wnt/p53 pathways influence lung adenocarcinoma phenotypes, including proliferation, apoptosis, and cell cycle progression. The EGFR-mutant setting allows investigation of JADE1’s potential impact on response to EGFR inhibitors like osimertinib, making this model valuable for studying epigenetic and signaling drivers of NSCLC pathogenesis and drug resistance. Moreover, JADE1??s role in DNA replication licensing suggests that its loss may affect replication stress responses, which is particularly relevant in cancer cells with high genomic instability.
These knockout cells are suited for western blotting (JADE1, acetyl-H4), RT-qPCR (Wnt targets), proliferation (MTS) and apoptosis (Annexin V/PI) assays, cell cycle analysis (PI staining), TOPFlash reporter assays, and osimertinib drug sensitivity testing. The polyclonal format provides a robust tool for mechanistic and functional studies of JADE1 in lung cancer. Researchers can thus systematically dissect JADE1-dependent epigenetic regulation and signaling pathways in a defined EGFR-mutant context. For further details, contact Ascent Research.
