The IGF2 Knockout SK-OV-3 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the SK-OV-3 human ovarian adenocarcinoma cell line. This product carries a targeted disruption of the IGF2 gene introduced via CRISPR/Cas9 genome editing, generating a loss-of-function model that abrogates endogenous IGF2 expression. The polyclonal nature of the knockout population reflects a heterogeneous mixture of edited alleles, providing a robust tool for studying IGF2-dependent phenotypes without clonal selection bias.
The SK-OV-3 host cell line was originally established from the ascitic fluid of a patient with ovarian adenocarcinoma. These epithelial cells harbor a well-characterized TP53 mutation, rendering them deficient in p53 tumor suppressor function, and they overexpress the HER2/neu oncogene. SK-OV-3 is widely employed as a model of high-grade serous ovarian cancer, exhibiting aggressive growth characteristics and serving as a platform for investigating oncogenic signaling and therapeutic resistance.
IGF2 encodes insulin-like growth factor 2, a potent mitogen that signals via IGF1R and insulin receptor isoform A. Its expression is epigenetically imprinted and transcriptionally regulated by E2F3 and PLAG1, with bioavailability modulated by IGFBP3 and IGFBP4. Receptor engagement activates the PI3K/AKT and MAPK/ERK pathways, recruiting effectors such as AKT1, mTOR, ERK1/2, BAD, GSK3B, FOXO, and S6K. Canonical signaling cascades include IGF2 ?? IGF1R ?? IRS1 ?? PI3K ?? AKT ?? mTOR ?? S6K for protein synthesis and IGF2 ?? IGF1R ?? SHC ?? GRB2 ?? SOS ?? RAS ?? RAF ?? MEK ?? ERK for proliferation. IGF2 also interacts with the clearance receptor IGF2R. Disruption of IGF2 in SK-OV-3 cells abolishes autocrine/paracrine stimulation, reducing AKT and ERK phosphorylation and impairing proliferation, survival, and metabolic activity.
In the SK-OV-3 ovarian cancer context, IGF2 contributes to oncogenic processes including unchecked proliferation, evasion of apoptosis, and metabolic reprogramming. Given the host cell’s TP53 mutation and HER2 overexpression, this knockout model enables dissection of IGF2-specific contributions amidst a background of other deregulated pathways. It is particularly relevant for research into ovarian cancer pathogenesis and for exploring the link between IGF2 dysregulation and syndromes such as Beckwith-Wiedemann (IGF2 overexpression) and Silver-Russell syndrome (IGF2 downregulation), as well as broader growth disorders and metabolic syndrome.
Researchers can employ this polyclonal knockout cell pool to investigate IGF2-dependent mechanisms in ovarian cancer, evaluate therapeutic targets, and study growth factor signaling and drug resistance. Typical experimental readouts include western blotting for phosphorylated AKT (S473) and phosphorylated ERK (T202/Y204), MTS or MTT proliferation assays, flow cytometric detection of apoptosis using Annexin V, migration and invasion assays using Boyden chambers, quantitative RT-PCR for downstream transcriptional targets, and colony formation assays to assess clonogenic growth. This IGF2 knockout model provides a versatile platform for functional validation experiments. For inquiries about this product, please contact Ascent Research.
