The IGF2 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population derived from the human clear cell renal cell carcinoma (ccRCC) cell line 786-O, designed to disrupt the IGF2 gene. This loss-of-function model eliminates insulin-like growth factor 2 (IGF2) expression, enabling study of IGF2-dependent signaling and tumorigenic processes. The polyclonal knockout strategy generates a heterogeneous population with targeted gene disruption, suitable for assessing mean population effects without clonal selection artifacts, providing a robust system for renal cancer research.
The parental 786-O cell line was established from a primary renal adenocarcinoma of a male patient with clear cell histology and is widely used as an epithelial model for ccRCC. These cells retain key disease features, including VHL inactivation, and exhibit robust IGF2 expression, making them ideal for interrogating growth factor signaling. The 786-O line offers a reproducible and translationally relevant platform for mechanistic and pharmacological studies.
IGF2 is a fetal growth factor that signals primarily through the IGF1 receptor (IGF1R) and the insulin receptor. Ligand binding triggers phosphorylation of insulin receptor substrate 1 (IRS1), activating the PI3K/Akt and MAPK/ERK cascades. Key downstream effectors include mTOR and ERK1/2, which drive cell proliferation and survival. IGF2 expression is regulated by growth hormone, insulin, and the H19 lncRNA, with transcription factors CTCF and SP1. The signaling network involves interactions with IGF2R, IGF-binding proteins, and adapter proteins Shc and Grb2. In 786-O cells, autocrine IGF2 production maintains tonic pathway activation, promoting malignant behavior.
CRISPR-mediated IGF2 knockout in 786-O cells disrupts this autocrine loop, reducing Akt and ERK1/2 phosphorylation and impairing proliferation and survival. This model mimics the effects of pharmacologic IGF1R inhibition and enables dissection of IGF2??s specific contributions to ccRCC. The system is relevant for studying growth abnormalities, Beckwith-Wiedemann syndrome, and IGF2 dysregulation in renal, hepatocellular, and breast cancers, allowing isolation of IGF2-dependent oncogenic mechanisms.
This polyclonal knockout product is suited for functional assays including western blotting and RT-qPCR to confirm IGF2 loss, MTT and BrdU incorporation for proliferation, annexin V for apoptosis, and phospho-Akt/ERK flow cytometry. It supports migration studies and drug sensitivity testing with IGF1R inhibitors, facilitating target validation and mechanistic studies. For further information, please contact Ascent Research.
