The ING2 Knockout NCI-H1975 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal population of NCI-H1975 lung adenocarcinoma cells in which ING2 has been disrupted. This heterogeneous knockout pool provides a loss-of-function model suitable for population-level studies, avoiding clonal artifacts while preserving genetic diversity.
The host cell line, NCI-H1975, is a human lung adenocarcinoma epithelial model derived from a female patient and harbors activating EGFR L858R and T790M mutations. These oncogenic mutations drive constitutive signaling and are clinically relevant in non-small cell lung cancer, making the line a gold-standard model for studying EGFR-targeted therapy and resistance.
ING2 functions as a tumor suppressor through its role as a stable subunit of the Sin3A/HDAC transcriptional corepressor complex. It directly interacts with SIN3A, HDAC1, HDAC2, SAP30, and BRMS1, and is recruited to chromatin by association with TP53. ING2 transcription is regulated by upstream signals including TP53, TGFB1, E2F1, and MYC. Mechanistically, ING2 promotes p53 acetylation and transactivation of CDKN1A (p21) and BAX, leading to cell cycle arrest and apoptotic cell death. Additionally, ING2 suppresses NF-kappaB transcriptional programs, providing a link between histone deacetylation and inflammatory signaling. By modulating chromatin structure and gene expression, ING2 plays a critical role in DNA damage responses and TGF-beta/BMP pathway crosstalk.
Disruption of ING2 in the NCI-H1975 background eliminates a key tumor suppressor within a model of mutant EGFR-driven lung adenocarcinoma. Given the role of ING2 in p53-dependent apoptosis and growth arrest, its knockout is anticipated to impair DNA damage responses and promote cell survival and proliferation, potentially mimicking oncogenic cooperativity observed in NSCLC. This polyclonal knockout model allows researchers to investigate how ING2 loss influences sensitivity to EGFR tyrosine kinase inhibitors, alters chromatin landscape through Sin3/HDAC complex dysregulation, and impacts crosstalk between growth factor signaling and tumor suppressive epigenetic mechanisms. It serves as a versatile system for dissecting ING2 function in the context of established oncogenic mutations.
This ING2 knockout cell pool is suitable for a wide range of applications including functional genomics screens, epigenetic regulation studies, and investigations of cancer drug resistance. Typical assays include western blotting and RT-qPCR for validating gene disruption and downstream target expression, RNA-seq for transcriptome-wide analysis, and ChIP-qPCR for examining Sin3/HDAC complex localization at specific promoters. Functional readouts such as colony formation, apoptosis assays, and cell cycle analysis enable phenotypic assessment of proliferation and survival. Drug sensitivity testing with EGFR inhibitors (e.g., osimertinib) or HDAC inhibitors can be conducted to evaluate therapeutic vulnerabilities. For further details or to discuss customized services, please contact Ascent Research.
