The IGF2 Knockout UM-UC-3 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the UM-UC-3 human bladder cancer cell line. This product provides a heterogeneous pool of cells with targeted disruption of the IGF2 gene, enabling loss-of-function investigations into insulin-like growth factor 2 signaling. The polyclonal format ensures a broad representation of gene-editing events, yielding a robust experimental system for functional genomics and pathway analysis without the constraints of single-cell clonal expansion.
The UM-UC-3 host cell line was established from a male patient with transitional cell carcinoma of the urinary bladder. As a well-characterized epithelial cancer model, UM-UC-3 cells retain molecular hallmarks of aggressive bladder malignancies, including constitutive activation of receptor tyrosine kinase cascades and aberrant growth factor signaling. These cells form a relevant background for examining the specific contributions of IGF2 to tumor cell proliferation, survival, and differentiation in a bladder cancer context.
IGF2 is a mitogenic polypeptide that functions predominantly through the type 1 insulin-like growth factor receptor (IGF1R) and the insulin receptor isoform A, with its bioactivity fine-tuned by IGF-binding proteins (IGFBP1?C6) and attenuated by the clearance receptor IGF2R. Ligand engagement triggers the PI3K-AKT and MAPK/ERK pathways, leading to phosphorylation and activation of core kinases such as AKT1 and MAPK1/3 (ERK1/2), and downstream effectors including mTOR, BAD, cyclin D1, and MYC that collectively drive cell cycle progression and suppress apoptosis. IGF2 expression is tightly regulated by an imprinted locus under the control of the long noncoding RNA H19, the chromatin organizer CTCF, and transcription factors including PLAG1, E2F family members, and WT1, forming a network that links developmental growth to oncogenic processes.
In bladder cancer, elevated IGF2 levels have been associated with enhanced proliferative capacity and resistance to therapy. Disrupting IGF2 in the UM-UC-3 background therefore creates a powerful tool for dissecting autocrine and paracrine loops that sustain malignant phenotypes. Additionally, because the IGF2-H19 imprinted domain is often dysregulated in cancer, these polyclonal knockout cells are suitable for studying epigenetic mechanisms and the consequences of imprinting loss. The reduction in AKT and ERK pathway activity following IGF2 ablation also makes this model valuable for validating small-molecule inhibitors targeting IGF1R and downstream kinases.
Typical research applications include cancer cell proliferation studies, growth factor signaling research, epigenetic imprinting investigations, tumor xenograft models, and drug target validation, particularly for IGF1R inhibitors. Supporting functional assays such as MTT/BrdU proliferation, Annexin V apoptosis, cell cycle analysis, soft agar colony formation, and Transwell migration/invasion can be employed, complemented by molecular analyses like western blotting, RT-qPCR, and RNA-seq. In vivo xenograft tumor growth studies using this knockout model facilitate evaluation of tumorigenic potential and therapeutic response. For further technical details or customization inquiries, please contact Ascent Research.
