IGF2 Knockout MCF-7 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population with targeted disruption of the IGF2 gene in the human MCF-7 breast adenocarcinoma cell line. The polyclonal pool encompasses a heterogeneous collection of IGF2 loss-of-function edits, enabling robust study of IGF2 deficiency without clonal selection artifacts. This model is designed for investigating IGF2-dependent signaling in an estrogen receptor-positive (ER+) breast cancer context.
The MCF-7 cell line was established from a metastatic pleural effusion of invasive ductal carcinoma and is classified as luminal A, ER-positive breast cancer. It harbors wild-type p53 and a natural caspase-3 deficiency, making it a widely used model for hormone-responsive tumor biology and apoptosis evasion studies. Its epithelial phenotype and well-defined signaling landscape facilitate detailed mechanistic research.
IGF2 encodes a fetal growth factor that activates IGF1R and insulin receptor isoform A (IR-A), stimulating the PI3K/AKT/mTORC1 and MAPK/ERK cascades. Downstream phosphorylation of AKT1 and ERK1/2 drives mTORC1-mediated upregulation of cyclin D1, BAD inhibition, and GLUT4 translocation, promoting proliferation, survival, and metabolism. IGF2 expression is positively regulated by estrogen, PLAG1, and HMGA2 and is subject to imprinting control at the H19/IGF2 locus. Extracellular IGF2 bioavailability is modulated by IGFBP1-6 and the IGF2R clearance receptor. Disruption of IGF2 abolishes ligand-receptor activation, thereby attenuating both AKT and ERK signaling and impairing oncogenic phenotypes.
In ER+ MCF-7 cells, IGF2 is implicated in growth stimulation and endocrine therapy resistance. Estrogen-driven IGF2 expression establishes a feed-forward loop that sustains proliferation even in low-hormone conditions. Knockout of IGF2 allows dissection of its autocrine/paracrine contribution to cell survival and proliferation independently of estrogen receptor activity, while the caspase-3 deficiency highlights reliance on IGF1R/IR-A survival signals.
The knockout cells support functional genomics, proliferation (MTS/BrdU) and apoptosis (Annexin V) assays, phospho-protein Western blotting, RT-qPCR, RNA-seq, colony formation, and xenograft tumor studies. They are particularly useful for drug sensitivity testing with IGF1R inhibitors and for exploring mechanisms of endocrine resistance in breast cancer. For additional technical details or support, please contact Ascent Research.
