The IGFBP7 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1975 human lung adenocarcinoma cell line, with targeted disruption of the IGFBP7 gene. This gene-edited pool allows researchers to investigate the loss-of-function consequences of IGFBP7 in a heterogeneous cell population, avoiding clonal selection artifacts.
The NCI-H1975 cell line is a well-characterized model of non-small cell lung cancer (NSCLC) harboring activating EGFR L858R and TP53 R273H mutations, which drive oncogenic signaling and impair p53-mediated tumor suppression. Originally isolated from an adenocarcinoma patient, these cells exhibit typical epithelial morphology and are widely employed to study kinase inhibitor resistance, apoptosis regulation, and metastatic behavior in lung cancer.
IGFBP7 encodes a secreted insulin-like growth factor-binding protein that acts as a tumor suppressor in multiple tissues. It directly binds IGF-I, IGF-II, and insulin, thereby inhibiting IGF1R activation and downstream AKT signaling. Additionally, IGFBP7 is transcriptionally activated by TP53 and TGF-beta1/SMAD pathways, and it promotes cellular senescence through upregulation of the cyclin-dependent kinase inhibitor CDKN1A (p21). The protein also induces apoptosis by modulating the BCL2/BAX ratio and suppresses angiogenesis through VEGFA downregulation. In the knockout model, disruption of IGFBP7 eliminates its negative regulation of IGF1R/IRS1/AKT signaling, impairs TGF-beta-mediated SMAD2/3 activation, and attenuates p21 expression, collectively enhancing cell proliferation and survival.
In the NCI-H1975 background, deletion of IGFBP7 provides a powerful tool to dissect its tumor-suppressive functions in an NSCLC model with concurrent EGFR and TP53 mutations. Since IGFBP7 is known to mediate p53-dependent senescence and apoptosis, its loss cooperates with the pre-existing TP53 R273H mutation to further disable growth suppressive mechanisms, potentially mimicking aggressive tumor phenotypes. This system enables precise evaluation of how IGFBP7 modulates response to EGFR-targeted therapies, as its loss may confer resistance by reactivating PI3K/AKT signaling. Moreover, the polyclonal nature of the knockout pool preserves the inherent heterogeneity of cancer cell populations, allowing assessment of gene function across diverse genetic subclones.
Researchers can utilize these cells to investigate tumor suppressor mechanisms, study IGF signaling and drug resistance, and conduct senescence and apoptosis assays. Typical downstream experiments include Western blotting for IGFBP7, phospho-IGF1R, AKT, SMAD2, p21, and BAX; RT-qPCR for target gene expression; Annexin V/PI apoptosis assays; senescence-associated beta-galactosidase staining; and Transwell migration/invasion assays. Co-immunoprecipitation can validate interactions between IGFBP7 and its binding partners. This model is also valuable for anti-angiogenic therapy research and metastasis studies. For further inquiries regarding this product, please contact Ascent Research.
