The IGF2 Knockout NCI-H1703 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1703 lung squamous cell carcinoma line. This product introduces a heterogeneous disruption of the IGF2 gene via targeted Cas9-mediated cleavage, generating a loss-of-function pool suitable for studying gene function without clonal selection artifacts. The polyclonal format preserves biological variance and facilitates robust, population-level analyses of IGF2-dependent phenotypes in a disease-relevant epithelial model.
The NCI-H1703 host cell line is an epithelial model of non-small cell lung cancer (NSCLC), originally established from a primary lung squamous cell carcinoma of a male patient. It recapitulates key features of the squamous subtype, including adherent growth and tumor formation in xenograft assays, and is widely employed for investigating oncogenic signaling pathways, drug response mechanisms, and metastatic progression in lung cancer research.
IGF2 encodes a fetal growth factor that binds to the type 1 insulin-like growth factor receptor (IGF1R) and insulin receptor isoform A (IR-A). Receptor engagement recruits adaptor proteins IRS1 and SHC, which activate the PI3K/AKT/mTOR cascade through AKT1 and mTOR, and the MAPK/ERK pathway via MAPK1/ERK2 and MAPK3/ERK1, thereby promoting proliferation, survival, and differentiation. Upstream regulation involves the H19-IGF2 imprinted locus, the chromatin organizer CTCF, growth hormone, prolactin, and transcription factors SP1 and AP-1. Additionally, IGF2 bioavailability is modulated by binding to IGFBP3 and the clearance receptor IGF2R/mannose 6-phosphate receptor.
In NCI-H1703 cells, endogenous IGF2 contributes to autocrine/paracrine loops that sustain oncogenic properties. Knockout of IGF2 disrupts ligand-dependent activation of IGF1R and IR-A, attenuating both PI3K/AKT/mTOR and MAPK/ERK signaling, leading to reduced proliferation, increased apoptosis, and impaired migration and invasion. This polyclonal knockout model therefore enables dissection of IGF2 dependency in lung squamous carcinoma and related malignancies such as colorectal cancer, Wilms tumor, and Beckwith-Wiedemann syndrome.
Researchers can employ the IGF2 Knockout NCI-H1703 Polyclonal Cells for functional genomics, drug target validation, and biomarker studies. Assays include western blotting, RT-qPCR, MTT and colony formation proliferation assays, Annexin V apoptosis detection, transwell migration/invasion, phospho-flow cytometry for p-AKT and p-ERK, and xenograft tumor models. These polyclonal cells are also suitable for high-content screening. For additional information, please contact Ascent Research.
