The IL17RA Knockout NCI-H1975 Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1975 human lung adenocarcinoma cell line. This polyclonal knockout pool carries targeted disruption of the IL17RA gene locus, generating a loss-of-function model that abolishes functional interleukin-17 receptor A expression without introducing a defined clonal genotype. The heterogeneous population retains the parental cell line??s epithelial characteristics and tumorigenic background while lacking IL17RA-mediated signaling, providing a versatile tool for pooled loss-of-function screening and functional genomics studies in a non-small cell lung cancer (NSCLC) context. The polyclonal format avoids clonal selection artifacts and preserves population-wide diversity, making the cells suitable for experiments requiring robust representation of knockout effects across multiple genetic backgrounds.
The host NCI-H1975 cell line was established from a non-smoking female patient with lung adenocarcinoma and harbors endogenous EGFR L858R and TP53 mutations, two hallmark genomic alterations in NSCLC. These cells serve as a well-characterized epithelial model for studying oncogenic signaling, drug resistance mechanisms, and tumor microenvironment interactions in a clinically relevant TP53-mutant, EGFR-driven adenocarcinoma background. The NCI-H1975 line is widely employed in preclinical cancer research for evaluating targeted therapies and dissecting pathways that contribute to tumor progression and immune evasion, providing a physiologically relevant cellular context for interrogating the role of IL-17RA in lung cancer biology.
IL17RA encodes the interleukin-17 receptor A, a transmembrane receptor that, upon binding to its ligands IL-17A or IL-17F, heterodimerizes with IL-17RC and recruits the adaptor protein Act1 (TRAF3IP2). This receptor?Cadaptor complex serves as a signaling hub that triggers downstream activation of TRAF6 and TAK1, leading to the engagement of the IKK complex and subsequent activation of NF-??B, as well as stimulation of p38 MAPK and JNK cascades. These pathways converge on transcription factors such as C/EBP?? to promote the expression of pro-inflammatory cytokines and chemokines, including IL-6, CXCL8, TNF, CSF2, and CCL20. The IL17RA signaling axis thus functions upstream of NF-??B and MAPK modules to coordinate inflammatory gene programs, and its disruption in this knockout model abrogates these downstream transcriptional responses.
In the context of the NCI-H1975 lung adenocarcinoma model, IL-17RA knockout provides a unique platform to dissect the contribution of IL-17?Cdriven inflammation to tumor progression. IL-17 signaling has been implicated in fostering a pro-tumorigenic microenvironment by promoting cytokine secretion, immune cell recruitment, and matrix remodeling, processes that are particularly relevant in EGFR-mutant NSCLC harboring p53 deficiency. By eliminating IL-17RA-mediated responses, these knockout cells enable the study of how loss of IL-17 pathway activity impacts tumor cell-intrinsic signaling, crosstalk with stromal components, and sensitivity to chemotherapeutic or targeted agents. The model is therefore valuable for investigating mechanisms of inflammation-driven tumor progression and for evaluating the therapeutic potential of targeting the IL-17 axis in lung cancer.
This IL17RA knockout polyclonal cell population can be applied in a wide range of functional assays, including Western blotting, RT-qPCR, ELISA-based cytokine profiling, and flow cytometric analysis of receptor expression. It supports phospho-signaling analysis to assess MAPK and NF-??B pathway activation status, NF-??B reporter assays to monitor transcriptional activity, and cell viability or migration/invasion assays to evaluate phenotypic consequences of IL-17RA loss. The cells are also suitable for pooled RNA-seq studies to characterize transcriptome-wide changes and for screening campaigns aimed at identifying IL-17 pathway inhibitors. This knockout model thus serves as a rigorous in vitro system for lung cancer research and immunological studies. For additional technical details or inquiries, please contact Ascent Research.
