The HRH1 Knockout SK-OV-3 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed to disrupt functional expression of the HRH1 gene in the SK-OV-3 human ovarian adenocarcinoma cell line. This loss-of-function model is generated via CRISPR/Cas9-mediated gene disruption, yielding a heterogeneous pool of knockout variants that collectively abolish HRH1 signaling. Polyclonal populations avoid clonal artifacts and are suitable for bulk functional genomics studies. The product provides a ready-to-use cellular system for investigating histamine receptor biology in an oncogenic context.
The SK-OV-3 parental line is derived from ascitic fluid of a 64-year-old Caucasian female with ovarian adenocarcinoma and exhibits adherent epithelial morphology. As an established model of epithelial ovarian cancer, SK-OV-3 cells recapitulate invasive growth and aberrant signaling. They are widely used to study oncogenic pathways, chemotherapeutic responses, and peritoneal dissemination. Their ascites origin is particularly relevant for investigating interactions between ovarian tumor cells and the histamine-rich peritoneal microenvironment.
HRH1 is a Gq/11-coupled GPCR that binds histamine to activate phospholipase C?? (PLC??), generating IP3 and DAG. IP3 mobilizes intracellular Ca2+, while DAG activates protein kinase C (PKC). These signals converge on the MAPK/ERK cascade, leading to ERK1/2 phosphorylation and activation of transcription factors NF-??B, AP-1, and CREB, which drive pro-inflammatory and proliferative gene expression. Receptor activity is modulated by GRK2/3-mediated phosphorylation and ??-arrestin1/2 recruitment, which desensitize G protein signaling and scaffold additional effectors. Thus, HRH1 translates extracellular histamine into coordinated cellular responses.
Disrupting HRH1 in SK-OV-3 provides a relevant model to study histamine signaling in ovarian cancer. The peritoneal environment contains elevated histamine from mast cells, and HRH1 activation in ovarian cancer cells has been linked to proliferation, calcium-dependent migration, and secretion of pro-angiogenic factors. This knockout model enables specific attribution of these phenotypes to HRH1 activity and dissection of crosstalk between Gq/11-coupled pathways and oncogenic ERK and NF-??B signaling in ovarian cancer cells, revealing potential therapeutic targets.
These HRH1 knockout polyclonal cells support diverse functional assays including calcium flux (Fluo-4), western blotting for phospho-ERK1/2, MTS/MTT proliferation, and Boyden chamber migration/invasion experiments. RT-qPCR and ELISA can profile downstream targets like IL-8 and COX-2. Applications include anti-histamine compound screening, ??-arrestin recruitment assays, and studies of allergic inflammation in cancer. This genetically defined system aids in exploring tumor microenvironment modulation and validating HRH1 as a therapeutic node. For additional information, please contact Ascent Research.
