The JAK2 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the 786-O human renal cell adenocarcinoma line. This product features a heterogeneous pool of cells with targeted disruption of the JAK2 gene, creating a loss-of-function model for studying JAK2-dependent processes. The polyclonal nature retains genetic diversity while abrogating JAK2 protein expression, enabling robust investigation of JAK2-mediated signaling without the constraints of single-cell clonal selection.
The parental 786-O cell line originates from a primary clear cell renal cell carcinoma (ccRCC) and serves as a widely employed model in renal cancer research. These adherent epithelial cells maintain characteristic features of ccRCC, including VHL inactivation and HIF pathway activation, providing a physiologically relevant background for examining oncogenic signaling networks. The 786-O line is particularly suited for dissecting the contributions of tyrosine kinases in renal tumorigenesis.
JAK2 encodes a non-receptor tyrosine kinase that functions as a central mediator of cytokine signaling. Upon ligand engagement of cytokine receptors such as EPOR, TPOR, GHR, and IFNGR, JAK2 is activated and phosphorylates downstream STAT transcription factors, notably STAT1, STAT3, and STAT5, which then dimerize and translocate to the nucleus to regulate gene expression. JAK2 also activates the PI3K-AKT and MAPK/ERK pathways through phosphorylation of adaptor proteins, promoting cell proliferation and survival. Key interacting partners include SH2B3 (LNK), SOCS proteins, and PTPN11 (SHP2), which modulate JAK2 activity and signal termination.
In the context of 786-O cells, JAK2 knockout disrupts the JAK-STAT signaling axis, potentially impairing cytokine-mediated growth and survival. Given the documented role of STAT3 and STAT5 in renal cell carcinoma progression, loss of JAK2 may attenuate oncogenic signaling downstream of interleukin and growth factor receptors. This polyclonal knockout model thus provides a powerful tool for examining the dependency of ccRCC cells on JAK2 for tumor maintenance and response to microenvironmental cytokines.
This product is ideally applied in studies of JAK2-dependent signaling in clear cell renal cell carcinoma, including functional analysis of the JAK-STAT pathway, investigation of cytokine-mediated proliferation and survival, and drug target validation for JAK inhibitors. Representative assays include western blotting for phospho-JAK2 and downstream STAT phosphorylation, RT-qPCR of JAK2 target genes, MTT cell proliferation assays, Annexin V apoptosis assays, interferon-gamma stimulation experiments, co-immunoprecipitation of JAK2 with cytokine receptors, and transwell migration/invasion assays. The polyclonal format supports large-scale screening and ensures robust, reproducible results across experiments. For further information, please contact Ascent Research.
