The GPRC5C Knockout NCI-H1975 Polyclonal Cells consist of a CRISPR/Cas9-edited polyclonal population derived from the NCI-H1975 lung adenocarcinoma line. This heterogeneous knockout model enables loss-of-function studies of the orphan class C GPCR GPRC5C in a cancer-relevant context. The polyclonal format maintains cellular diversity while disrupting the target gene, making it suitable for pooled functional screens and assays requiring bulk cell populations. The knockout cells retain the parental line??s EGFR L858R and T790M mutations, preserving their relevance to non-small cell lung cancer (NSCLC) research.
The NCI-H1975 parental cells, derived from a 64-year-old female patient, are a well-characterized human lung adenocarcinoma line with activating EGFR L858R and resistance-conferring T790M mutations. These cells exhibit constitutive MAPK/ERK and PI3K/Akt signaling typical of EGFR-mutant NSCLC. The adherent epithelial morphology and defined genetic background make NCI-H1975 an ideal host for investigating the interplay between GPRC5C function and oncogenic pathways. This context provides a clinically relevant platform for studying tumor cell biology and therapeutic vulnerabilities.
GPRC5C is a retinoic acid-inducible orphan GPCR that signals through Gi/Go proteins and ??-arrestin to modulate adenylyl cyclase activity and cAMP levels. Transcriptionally regulated by RAR/RXR heterodimers, it couples retinoic acid signals to downstream kinases including ERK1/2 and Akt. These pathways control proliferation, survival, and differentiation, positioning GPRC5C as a potential integrator of retinoid and growth factor signaling. The knockout in NCI-H1975 cells allows dissection of GPRC5C-dependent molecular events without confounding receptor activation.
Knockout of GPRC5C in NCI-H1975 cells offers a powerful tool to explore its role in lung adenocarcinoma, where it may influence drug response, cell proliferation, and metastatic potential. The polyclonal population is particularly useful for detecting heterogeneous phenotypic effects across a mixed gene-edited pool. Studies can address whether GPRC5C functions as a tumor suppressor or oncogene in NSCLC, and how it intersects with EGFR-driven signaling. This model also facilitates analyses of retinoic acid responsiveness and resistance mechanisms to targeted therapies.
Typical applications include immunoblotting and RT-qPCR for target and pathway validation, proliferation and colony formation assays, migration and invasion tests, and drug sensitivity profiling with EGFR inhibitors. The cells are suitable for RNA-seq transcriptomic analysis, luciferase reporter assays for retinoic acid pathway activity, and flow cytometry for signaling readouts. Researchers studying GPCR signaling, lung cancer biology, or retinoid pharmacology can leverage this model to uncover novel regulatory mechanisms. For additional information or customized gene-editing needs, please contact Ascent Research.
