The IL3 Knockout SK-HEP-1 Polyclonal Cells from Ascent Research are a CRISPR/Cas9-edited polyclonal knockout cell population with targeted disruption of the human IL3 gene in the SK-HEP-1 host cell line. This loss-of-function model supports investigation of IL-3 cytokine signaling in a liver adenocarcinoma context, applicable to signaling pathway dissection, functional genomics, and drug discovery.
SK-HEP-1 is a human liver adenocarcinoma line isolated from patient ascites, exhibiting endothelial-like morphology. Widely used in hepatocellular carcinoma and tumor microenvironment research, these adherent cells are amenable to CRISPR/Cas9 editing and downstream phenotypic analyses.
The IL3 gene encodes interleukin-3, a hematopoietic growth factor that promotes proliferation and differentiation of multipotent progenitors. IL-3 signals through a heterodimeric receptor composed of IL3RA and CSF2RB, activating JAK2 kinase to phosphorylate STAT5A/B transcription factors, while also recruiting GRB2/SHC1 to stimulate the MAPK cascade and PIK3R1 to trigger PI3K/AKT signaling. Downstream targets include MYC, CCND1, BCL2, PIM1, and SOCS1. Upstream regulators such as T cell receptor activation, IgE crosslinking, PMA, and calcium ionophore induce IL3 expression. In SK-HEP-1 cells, IL3 disruption eliminates autocrine/paracrine signaling, preventing activation of these proliferative and anti-apoptotic pathways.
This model enables dissection of IL-3 signaling in a solid tumor line that typically lacks high IL-3 expression, facilitating paracrine signaling studies via exogenous ligand or conditioned medium. Abrogating IL-3 allows assessment of cell proliferation, survival, and migration dependency, and crosstalk with cytokines sharing JAK/STAT and MAPK nodes. The polyclonal population reduces clonal bias and provides a representative response. This approach broadens investigation of hematopoietic cytokine functions in epithelial tumors and the tumor microenvironment.
Applications include screening for IL-3 pathway inhibitors, validating IL3 receptor presence in non-hematopoietic cells, and examining hematopoietic cytokine crosstalk in solid tumor contexts. Assays like phospho-STAT5 western blotting, RT-qPCR, flow cytometry for IL3RA/CSF2RB surface expression, MTS/BrdU proliferation, and Annexin V apoptosis profiling are readily compatible. For more information or to request a quote, please contact Ascent Research.