The JAG2 Knockout T-47D Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population designed to disrupt human JAG2 expression, creating a loss-of-function model in T-47D breast cancer cells. The polyclonal format consists of a pool of edited cells with heterogeneous genomic modifications at the JAG2 locus, ensuring a representative range of functional knockouts without clonal selection bias. This product is optimized for functional genomics studies requiring robust disruption of JAG2-mediated signaling pathways.
The parental T-47D line is a human breast ductal carcinoma epithelial cell line derived from a pleural effusion of a 54-year-old female with metastatic invasive ductal carcinoma. T-47D cells are ER+, PR+, and AR+, making them a standard model for hormone receptor-positive luminal breast cancer. Their well-defined hormone sensitivity and molecular profile make them particularly suitable for investigating signaling networks that interface with steroid hormone pathways.
JAG2 acts as a ligand for NOTCH1?C4 receptors, mediating cell?Ccell communication through a juxtacrine mechanism. Ligand?Creceptor engagement triggers sequential cleavage by ADAM10 and ??-secretase, releasing the NICD. NICD translocates to the nucleus to form a complex with CSL/RBPJ and MAML, directly activating transcription of targets like HES1, HEY1, MYC, and CCND1. Upstream, JAG2 expression is controlled by MYC, TP53, and TGFB1, and signaling is fine-tuned by endocytic regulators NUMB and DTX. This positions JAG2 at a node connecting growth factor and Notch pathways, influencing proliferation and differentiation.
In T-47D cells, JAG2 disruption provides a system to dissect Notch-dependent mechanisms in ER+ breast cancer, where aberrant Notch activity contributes to tumor initiation, maintenance of cancer stem cells, and therapy resistance. Co-targeting of Notch and hormone pathways is an emerging therapeutic strategy, and this knockout model enables assessment of JAG2??s specific contribution to estrogen-independent growth and metastatic behavior. Additionally, it offers a tool for exploring broader JAG2-related pathologies, including developmental anomalies like Alagille syndrome, given the gene??s conserved roles.
Researchers can employ this polyclonal knockout population for detailed pathway analysis using western blotting of NICD and HES1, RT-qPCR for downstream transcripts, and luciferase reporter assays for Notch transcriptional output. Drug sensitivity testing with ??-secretase inhibitors, co-immunoprecipitation of Notch?CJAG2 complexes, and flow cytometric quantification of surface JAG2 are also feasible. Migration and invasion assays further extend utility to functional studies of tumor cell dissemination. For additional information, please contact Ascent Research.
