The ACE2 Knockout NCI-H1703 Polyclonal Cells consist of a polyclonal population of NCI-H1703 human lung squamous cell carcinoma cells in which the ACE2 gene has been disrupted via CRISPR/Cas9-mediated gene editing, generating a loss-of-function model. This heterogeneous knockout product format mitigates the risk of clonal artifacts and enables robust analysis of ACE2-dependent biological processes.
NCI-H1703 is an adherent epithelial cell line derived from a human lung squamous cell carcinoma, retaining key morphological and growth characteristics of malignant lung epithelium. As a widely used model in lung cancer research, it provides a clinically relevant background for investigating ACE2 function in oncogenic and viral contexts.
ACE2 is a critical regulator of the renin-angiotensin system, catalyzing the conversion of the vasoconstrictor angiotensin II to the vasodilator angiotensin-(1-7). The latter activates the Mas receptor, triggering downstream signaling cascades involving AKT, eNOS, and nitric oxide to promote vasodilation and anti-inflammatory responses. ACE2 expression is influenced by upstream regulators such as interferon-??/??, glucocorticoids, androgens, IL-1??, and TNF-??. Beyond its enzymatic role, ACE2 functions as the primary receptor for SARS-CoV-2 spike protein, with viral entry facilitated by TMPRSS2-mediated priming. ACE2 also forms complexes with B0AT1 (SLC6A19), Collectrin, and integrins, underscoring its pleiotropic functions.
In the NCI-H1703 lung squamous cell carcinoma background, disruption of ACE2 enables dissection of renin-angiotensin system contributions to tumor cell biology, including proliferation and inflammatory responses. This model is particularly valuable for studying SARS-CoV-2 viral entry and pathogenesis in a lung cancer context, addressing the heightened susceptibility observed in patients with pulmonary malignancies.
Representative experimental protocols enabled by these polyclonal knockout cells include SARS-CoV-2 pseudovirus entry assays to quantify viral uptake, angiotensin-(1-7) ELISA for monitoring renin-angiotensin system activity, and RNA-seq for transcriptome-wide analysis of ACE2-dependent gene expression. Additional techniques such as cell proliferation assays, flow cytometry, and Western blotting for AKT and eNOS phosphorylation provide complementary phenotypic and signaling readouts. These cells are ideal for COVID-19 drug screening, mechanistic studies in lung cancer biology, and epithelial cell function research. For further details, please contact Ascent Research.