The HDAC7 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited heterogeneous knockout pool of the human lung adenocarcinoma cell line NCI-H1975, with disruption of the histone deacetylase 7 (HDAC7) gene. Provided as polyclonal cells, this product enables loss-of-function studies in a clinically relevant EGFR-mutant non-small cell lung cancer (NSCLC) background without clonal selection.
NCI-H1975 is an adherent epithelial line derived from a non-small cell lung cancer patient. It harbors the EGFR L858R/T790M mutation, making it sensitive to EGFR tyrosine kinase inhibitors (TKIs), and maintains wild-type TP53 and KRAS, preserving key tumor suppressor and signaling pathways. This genetic profile renders NCI-H1975 a robust model for EGFR-driven lung adenocarcinoma research.
HDAC7 is a Class IIa histone deacetylase that represses MEF2-dependent transcription by directly binding MEF2 transcription factors (MEF2A, MEF2C, MEF2D) and assembling a corepressor complex with HDAC3 and SMRT/NCOR. Upstream signals including VEGF/VEGFR2, TGF-??, and Notch activate kinases such as PKD1 and Ca2+/calmodulin-dependent kinases, which phosphorylate HDAC7, inducing 14-3-3 binding and nuclear export to relieve repression. HDAC7 also interacts with HIF-1?? and ??-catenin, linking to hypoxia and Wnt pathways. Its downstream targets include NR4A1, CDKN1A, BCL2 family members, VEGF-A, and matrix metalloproteinases, thereby controlling apoptosis, angiogenesis, and cell migration.
In NCI-H1975 cells, HDAC7 knockout provides a platform to investigate its role in EGFR-mutant NSCLC pathogenesis, particularly in TKI resistance, metastasis, and angiogenesis. The polyclonal nature preserves population heterogeneity, allowing studies that more closely mirror tumor biology compared to clonal isolates.
Representative applications include western blotting for HDAC7 and histone acetylation; RT-qPCR of MEF2 targets (NR4A1, CDKN1A); ChIP-qPCR for HDAC7 binding; proliferation and apoptosis assays; Transwell migration/invasion; immunofluorescence for HDAC7 localization; co-IP of HDAC7-MEF2 complexes; RNA-seq; and EGFR TKI sensitivity testing. This model supports target validation, drug screening, and mechanistic studies in lung cancer. For further technical inquiries, contact Ascent Research.
