The JUN Knockout 143B Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout population derived from the human osteosarcoma cell line 143B, designed to disrupt the JUN gene. This product offers a heterogeneous pool of cells carrying diverse JUN-inactivating mutations, enabling robust loss-of-function studies without clonal artifacts. It provides a flexible platform for dissecting AP-1 transcription factor function in a tumorigenic background.
The parental 143B cell line is an adherent, epithelial-like human osteosarcoma model with wild-type TP53 status, widely used for its high tumorigenicity in xenograft assays. These osteoblastic-like cells retain key oncogenic signaling networks, making them a suitable host for studying the role of AP-1 in osteosarcoma biology. The 143B line is particularly valuable for investigating bone cancer proliferation, metastasis, and drug response.
JUN encodes c-Jun, a bZIP transcription factor that forms the AP-1 complex with partners like c-Fos, FosB, and ATF2. Phosphorylation at Ser63/73 by JNK1/2/3 (MAPK8/9/10), as well as ERK1/2 and p38 MAPK, activates c-Jun downstream of EGF, TNF-??, IL-1, and UV radiation. Active AP-1 complexes transcriptionally control genes such as Cyclin D1, c-Myc, MMP-1/3/9, and VEGF, governing proliferation, survival, and matrix remodeling. c-Jun also interacts with coactivators p300/CBP and transcription factors STAT3 and NFAT, integrating multiple signaling cascades.
In the context of 143B osteosarcoma cells, knockout of JUN disrupts AP-1 transcriptional activity, potentially attenuating oncogenic signals that drive tumor growth and invasion. Given that MAPK-JNK-c-Jun signaling is frequently hyperactive in osteosarcoma, this knockout model allows interrogation of pathway dependencies and identification of critical downstream effectors. The loss of c-Jun may impair the expression of proliferative and pro-survival genes, rendering cells more susceptible to apoptosis and targeted therapies. This makes the polyclonal JUN knockout population a relevant system for uncovering therapeutic vulnerabilities in bone cancer.
Researchers can employ this product in a range of applications, including mechanistic studies of AP-1-dependent transcription using luciferase reporters and RT-qPCR for target genes such as Cyclin D1 and MMP1. It is suitable for phenotypic assays like MTT/CCK-8 proliferation, Transwell migration/invasion, and Annexin V apoptosis analysis. Additionally, the knockout cells can be used to screen JNK pathway inhibitors (e.g., SP600125) and evaluate functional redundancy among Jun/Fos family members. In vivo, this model supports xenograft tumor growth studies to assess the impact of JUN loss on osteosarcoma progression. For additional details, please contact Ascent Research.
