The GNRH1 Knockout HGC-27 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population of HGC-27 human gastric carcinoma cells with disruption of the GNRH1 gene. This loss-of-function model eliminates gonadotropin-releasing hormone (GnRH) expression, enabling study of autocrine/paracrine GnRH signaling in gastric cancer. The polyclonal format reflects the heterogeneous edits generated across the cell population, providing a robust tool for pathway analysis without clonal selection.
The HGC-27 cell line was derived from a metastatic lymph node of a gastric cancer patient and serves as a well-characterized model for gastric adenocarcinoma pathogenesis and drug responsiveness. HGC-27 cells express endogenous GnRH signaling components, making them particularly relevant for investigating the role of GnRH in cancer cell behavior and hormone-mediated growth regulation.
GNRH1 encodes the hypothalamic decapeptide gonadotropin-releasing hormone. Upon binding to its receptor GNRHR, GnRH activates the Gq/11/phospholipase C pathway, triggering calcium mobilization and protein kinase C activation, which converges on the MAPK/ERK cascade to phosphorylate transcription factors such as CREB and AP-1. This signaling drives expression of gonadotropin subunits LHB and FSHB in the reproductive axis. In non-pituitary contexts, GnRH also modulates MAPK1/3 (ERK1/2) and CREB activity. GNRH1 transcription is regulated by upstream factors including KISS1, neurokinin B, and steroid hormones, while its bioactive peptide is processed by prohormone convertases PC1/3 and PC2. Disruption of GNRH1 in HGC-27 cells eliminates basal GnRH-driven MAPK/ERK signaling, providing a clean system to study pathway dependencies.
In gastric cancer, autocrine GnRH signaling has been implicated in tumor cell proliferation, migration, and drug resistance. The GNRH1 knockout in HGC-27 cells allows direct interrogation of these functions by comparing wild-type and GNRH1-disrupted populations. This model helps delineate how endogenous GnRH contributes to oncogenic signaling through MAPK/ERK and CREB, and may reveal vulnerabilities to GnRH analog-based therapies.
Typical applications include RT-qPCR and immunofluorescence to confirm GNRH1 disruption, western blotting for phospho-ERK1/2 to assess pathway activity, and functional assays such as proliferation and migration in the presence of GnRH analogs like leuprolide or cetrorelix. The polyclonal population is also suitable for co-culture experiments and drug screening to identify compounds that circumvent GnRH dependency. For technical inquiries, please contact Ascent Research.
