The JAK3 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human 786-O renal cell carcinoma cell line, engineered to disrupt JAK3 expression. This polyclonal pool enables rapid functional analysis of JAK3-dependent pathways without clonal isolation, providing a heterogeneous yet genetically defined model for studying loss-of-function phenotypes in a cancer-relevant epithelial background. The cells are supplied as a ready-to-use pool suitable for immediate culture and downstream assays.
The parental 786-O cell line originated from a primary clear cell adenocarcinoma of the kidney and serves as a canonical model for clear cell renal cell carcinoma (ccRCC). These adherent epithelial cells harbor a VHL frameshift mutation, leading to constitutive HIF pathway activation, a hallmark of ccRCC. 786-O cells exhibit robust proliferation, migratory capacity, and express relevant cytokine receptors, making them valuable for interrogating tumor-intrinsic signaling networks.
JAK3 is a non-receptor tyrosine kinase that associates with the common gamma chain (IL2RG) and is activated by cytokines IL-2, IL-4, IL-7, IL-15, and IL-21. Upon ligand binding, JAK3 is phosphorylated by upstream SRC kinases and cooperates with JAK1 to activate STAT5A, STAT5B, STAT3, and STAT6, which translocate to drive transcription of target genes such as MYC, BCL2L1, CCND1, and PIM1. Cross-talk with PI3K-AKT and MAPK pathways amplifies proliferative and survival signals, while SOCS1 provides feedback inhibition. In renal carcinoma, aberrant JAK3 activity can promote oncogenic growth and immune evasion.
In 786-O cells, CRISPR/Cas9-mediated disruption of JAK3 ablates cytokine-induced JAK-STAT signal transduction, impairing transcriptional activation of genes controlling cell cycle progression, apoptosis resistance, and immune modulation. Consequently, JAK3 knockout cells exhibit reduced proliferation, increased apoptotic sensitivity, and altered responses to cytokine-rich microenvironments, recapitulating a loss-of-function state critical for dissecting ccRCC biology and evaluating JAK-targeted therapies.
The JAK3 Knockout 786-O Polyclonal Cells support functional analysis of JAK3 in renal cancer, cytokine signaling studies, JAK inhibitor drug testing (e.g., tofacitinib), and tumor microenvironment research. Representative assays include Western blotting for phosphorylated STAT5/STAT3, RT-qPCR of MYC and BCL2L1, flow cytometry for apoptosis/cell cycle, MTT proliferation, RNA-seq transcriptomics, and migration/invasion assays. The polyclonal format offers experimental speed and population-level heterogeneity. For additional technical information, please contact Ascent Research.
