The IL3 Knockout 786-O Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal population originating from the 786-O human renal cell adenocarcinoma line in which the IL3 gene has been disrupted. This loss-of-function model provides a robust system for investigating the roles of interleukin-3 (IL3) in epithelial tumor biology, particularly within the context of clear cell renal cell carcinoma. The polyclonal nature ensures gene disruption across the cell pool while avoiding clonal selection effects, making it suitable for population-level functional studies.
The parental 786-O cell line is a well-characterized model of clear cell renal cell carcinoma. Derived from a primary renal adenocarcinoma, these epithelial cells harbor a mutated VHL tumor suppressor and are PTEN-null, leading to constitutive activation of hypoxia-inducible factor pathways and altered PI3K/AKT signaling. The line retains tumorigenic capacity in xenograft models and is widely employed in cancer research for studying VHL-dependent pathways, metastatic behavior, and therapeutic responses.
Interleukin-3 is a hematopoietic growth factor that signals through a heterodimeric receptor composed of IL3R?? (CD123) and the common beta chain (CSF2RB/CD131). Ligand binding activates JAK2, which phosphorylates STAT5, driving transcription of targets such as BCL2, MYC, and CCND1. Parallel pathways involve GRB2/SHC/SOS-mediated Ras activation, leading to Raf/MEK/ERK signaling, and PI3K-dependent AKT phosphorylation that regulates mTOR and FOXO. Upstream, IL3 expression is controlled by T-cell receptor-induced NFAT and AP-1 transcription factors, PKC signaling, CD28 costimulation, and inflammatory cytokines including IL-1 and TNF-alpha. Knockout of IL3 ablates these downstream networks, enabling dissection of cytokine-driven cascades.
In the 786-O cell line, ablation of IL3 enables investigation of autocrine or paracrine cytokine effects that may contribute to tumor microenvironment remodeling or immune evasion. Although IL3 is classically associated with hematopoietic differentiation, its ectopic expression in epithelial cancers can modulate intercellular communication with infiltrating immune cells. This knockout model thus provides a platform for dissecting how tumor-derived IL3 influences STAT5, PI3K, and MAPK signaling within carcinoma cells or in co-cultured stromal and immune populations.
This IL3 knockout product is suited for diverse research applications. Functional assays may include Western blotting, RT-qPCR, and RNA-seq for pathway validation; MTS/CCK-8 and Annexin V apoptosis assays for proliferation and survival analysis; ELISA for cytokine secretion; and Transwell migration/invasion assays. Immune context studies can employ phospho-STAT5 flow cytometry and co-culture systems with immune effector cells. In vivo tumorigenicity experiments using xenograft models further elucidate the role of IL3 in tumor progression. For further information, please contact Ascent Research.
