JAK2 Knockout 769-P Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population originating from the human renal cell carcinoma line 769-P, engineered for targeted disruption of the JAK2 gene. This knockout model provides a versatile loss-of-function platform for studying the roles of Janus kinase 2 in cytokine receptor signaling within a VHL-deficient cellular background. The polyclonal nature of the product reflects the mixed genetic outcomes of CRISPR/Cas9 editing, offering a population that includes JAK2-disrupted cells without clonal selection, suitable for experiments where population-level readouts are preferred.
The parental 769-P cell line is a widely used model of clear cell renal cell carcinoma (ccRCC) characterized by biallelic loss of the von Hippel-Lindau (VHL) tumor suppressor, resulting in constitutive stabilization of hypoxia-inducible factors (HIFs) and chronic activation of hypoxia-responsive gene programs. As an adherent epithelial line derived from a primary renal carcinoma, 769-P recapitulates key molecular features of VHL-deficient kidney cancer, making it particularly valuable for investigating oncogenic signaling cross talk and therapeutic vulnerabilities.
JAK2 is a non-receptor tyrosine kinase that functions downstream of numerous cytokine receptors, including the IL-6 receptor complex (IL-6R??/gp130), erythropoietin receptor (EPOR), thrombopoietin receptor, and growth hormone receptor. Ligand-induced receptor dimerization triggers JAK2 trans-phosphorylation and activation, leading to phosphorylation of STAT transcription factors (STAT1, STAT3, STAT5A, STAT5B). Activated STATs dimerize, translocate to the nucleus, and directly promote transcription of target genes such as BCL2L1 (BCL-XL), CCND1 (Cyclin D1), and MYC, which drive cell proliferation and survival. JAK2 also signals through the PI3K?CAKT and MAPK/ERK pathways via interaction with adaptor proteins GRB2 and PI3K regulatory subunit p85. Signaling is tempered by negative regulators SOCS1 and SOCS3, themselves JAK2-responsive genes that establish a feedback loop. Additionally, JAK2 signaling can intersect with the HIF-1 pathway, a critical node in VHL-deficient renal carcinoma.
In the context of 769-P VHL-null renal carcinoma cells, JAK2 knockout offers a unique model to dissect the interplay between cytokine-driven signaling and the dysregulated hypoxic response. The polyclonal knockout population enables examination of JAK2-dependent effects on cellular proliferation, survival, and apoptosis, as well as potential crosstalk between JAK2?CSTAT3/5 and HIF-mediated transcriptional programs. This system is particularly relevant for exploring how JAK2 activity may modulate tumorigenic phenotypes in ccRCC and for evaluating JAK2 as a therapeutic target in this malignancy.
This product is suitable for a broad range of experimental applications, including renal cell carcinoma signaling studies, JAK2 inhibitor screening, and cytokine response analysis. Representative assays include western blotting for phospho-JAK2 and phospho-STAT3/5, RT-qPCR quantification of SOCS3 and BCL2L1, MTT proliferation assays, co-immunoprecipitation of JAK2 with gp130, STAT-reporter luciferase assays, and phospho-flow cytometry. The JAK2 Knockout 769-P Polyclonal Cells thus provide a robust tool for fundamental cancer biology research and preclinical drug development. For further information or to discuss custom requirements, please contact Ascent Research.
