The GNRH1 Knockout LoVo Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population with disrupted GNRH1, the gene encoding gonadotropin-releasing hormone precursor. Derived from the LoVo human colorectal adenocarcinoma cell line, these pooled knockout cells enable loss-of-function studies without clonal selection. They are designed for investigating GnRH signaling in cancer biology and reproductive endocrinology.
LoVo cells were isolated from a lymph node metastasis of a 56-year-old male with Dukes’ type C colorectal adenocarcinoma. These epithelial cells serve as a well-characterized in vitro model for metastatic colon cancer, offering a clinically relevant background for gene knockout studies. Their stable growth in culture and retention of malignant features make them suitable for examining GNRH1 function.
GNRH1 encodes a preprohormone processed into the decapeptide GnRH, which binds GNRHR and activates Gq/11 (GNAQ/GNA11). This triggers PLCB-mediated hydrolysis of PIP2 to IP3 and DAG; IP3 mobilizes intracellular calcium, while DAG activates PKC (PRKCA). Downstream, the MAPK/ERK pathway is engaged via RAF, MEK, and ERK1/2 (MAPK1/3), phosphorylating transcription factors ELK1 and CREB, and promoting expression of JUN and FOS. In pituitary gonadotropes, this cascade induces LHB and FSHB, while in other contexts it can regulate steroidogenic enzymes (CYP11A1, HSD3B2). GnRH signaling is modulated by upstream inputs such as KISS1, neurokinin B, dynorphin, estradiol, testosterone, cortisol, and photoperiod signals, and is subject to feedback via arrestins. It also intersects with PI3K-Akt and calmodulin (CALM1) pathways. In cancer cells, autocrine GnRH influences proliferation and apoptosis through similar mechanisms.
In colorectal adenocarcinoma, autocrine/paracrine GNRH1 signaling may regulate tumor growth and survival. Disruption of GNRH1 in LoVo cells allows investigation of its role in processes like epithelial-mesenchymal transition, migration, and drug resistance. This model is valuable for studying the interplay between reproductive hormone pathways and colorectal cancer progression.
These polyclonal knockout cells are suitable for RT-qPCR, ELISA, western blotting (e.g., phospho-ERK1/2, JUN, FOS), and reporter assays to probe GnRH signaling. Functional studies include MTT/BrdU proliferation assays, caspase-3/7 apoptosis assays, Annexin V staining, and Boyden chamber migration/invasion assays. They also enable drug sensitivity testing with GnRH agonists or antagonists. For further information, please contact Ascent Research.
