The IGF2 Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population derived from the SK-HEP-1 human hepatic adenocarcinoma cell line, engineered to disrupt the IGF2 gene. This loss-of-function model enables the study of insulin-like growth factor 2 signaling without the constraints of clonal isolation, preserving the inherent heterogeneity of the parental cell line. The polyclonal knockout format provides a robust and efficient way to interrogate gene function in a pool of genetically modified cells, minimizing clonal artifacts.
SK-HEP-1 cells were originally isolated from the ascitic fluid of a male patient with adenocarcinoma of the liver and serve as a widely used model for hepatocellular carcinoma (HCC). These cells exhibit characteristic features of liver cancer, including rapid proliferation, anchorage-independent growth, and tumor formation in xenograft models, making them a relevant system to investigate HCC biology and therapeutic responses.
IGF2 encodes a potent mitogen that acts as a secreted ligand, binding primarily to the IGF1 receptor (IGF1R) and insulin receptor isoform A to activate downstream signaling. Receptor tyrosine kinases recruit adaptors such as IRS1 and IRS2, leading to activation of the PI3K-AKT and RAS-MAPK pathways. Key effectors include AKT, mTOR, ERK1/2, and cell cycle regulators that drive proliferation, survival, and metabolism. IGF2 expression is regulated by upstream factors including PLAG1, WT1, and CTCF, and is subject to parental imprinting with maternal allele silencing. Disruption of IGF2 abolishes autocrine/paracrine ligand availability, attenuating IGF1R-mediated signal transduction and reducing phosphorylation of AKT and ERK.
In the context of hepatocellular carcinoma, IGF2 is frequently overexpressed and contributes to oncogenic transformation, tumor growth, and resistance to apoptosis. The SK-HEP-1 knockout model therefore provides a physiologically relevant platform to dissect the contribution of IGF2 to liver cancer progression. By eliminating IGF2 production, researchers can assess its role in sustaining malignant phenotypes, including cell cycle progression, migration, and colony formation, and explore compensatory signaling mechanisms that may emerge in the absence of this key growth factor.
This polyclonal knockout population is suitable for functional analysis of IGF2 in liver cancer, screening inhibitors targeting the IGF1R/PI3K/AKT/mTOR axis, and investigating epigenetic regulation of imprinted genes. Typical assays include Western blotting, RT-qPCR, proliferation and apoptosis assays, phospho-AKT/ERK analysis, RNA-seq, migration, and colony formation assays. For additional information, contact Ascent Research.
