The IGFBP7 Knockout A-549 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human A-549 lung adenocarcinoma cell line. This product features disruption of the tumor suppressor gene IGFBP7, providing a versatile loss-of-function model for dissecting signaling pathways and phenotypes in non-small cell lung cancer. The polyclonal format captures a spectrum of edited variants, avoiding clonal bias and enabling robust functional genomic studies.
The parental A-549 cell line was established from a 58-year-old Caucasian male with lung adenocarcinoma and serves as a model for type II alveolar epithelial cells. Widely used in NSCLC research, these cells harbor an activating KRAS mutation and are employed to investigate proliferation, apoptosis, migration, and drug response. The well-characterized background makes A-549 an ideal host for examining the consequences of IGFBP7 loss.
IGFBP7 encodes a tumor suppressor transcriptionally activated by p53 and oncogenic RAS/BRAF. It binds IGF1 and IGF2 with low affinity and modulates integrin-mediated adhesion. Mechanistically, IGFBP7 inhibits ERK and AKT signaling, upregulates CDK inhibitors p21 and p16, and downregulates cyclin D1, MMP-2, and MMP-9. This leads to suppressed angiogenesis, promoted senescence and apoptosis, linking growth factor signaling to cell cycle arrest.
In A-549 cells, which possess an activating KRAS mutation, IGFBP7 loss disrupts p53- and RAS-dependent tumor suppression. Additionally, TGF-beta and retinoid signaling pathways converge on IGFBP7 regulation, making this knockout model valuable for examining cross-talk between growth factor and differentiation cues. The polyclonal population facilitates studies of senescence evasion, apoptosis resistance, and drug response to RAS-RAF-MEK-ERK and PI3K-AKT pathway inhibitors.
Typical applications include Western blotting and RT-qPCR for pathway analysis, senescence-associated ??-galactosidase assays, caspase-3/7 apoptosis assays, and Transwell migration/invasion assays. Proliferation assays and RNA-seq enable comprehensive phenotyping. Immunofluorescence and co-immunoprecipitation can examine interactions with extracellular matrix proteins. The product is suitable for biomarker discovery and drug resistance studies. For further information, contact Ascent Research.
