The GPER1 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population that provides a loss-of-function model for the GPER1 gene in the 786-O renal cell carcinoma background. Generated through CRISPR/Cas9-mediated gene disruption, this polyclonal pool enables robust population-level studies without the potential bias of single-cell clones, making it ideal for investigating GPER1-dependent signaling and functional responses.
The 786-O cell line is a well-characterized human clear cell renal cell carcinoma model originally established from a primary tumor of a 58-year-old male. These cells harbor a VHL tumor suppressor mutation, leading to constitutive HIF pathway activation and reflecting the genetic and molecular features of clear cell RCC. The line is widely adopted for mechanistic and therapeutic studies in kidney cancer research.
GPER1 functions as a membrane-bound G protein-coupled receptor that transduces rapid estrogen signals. Ligand activation by estradiol, estrogenic compounds, or the selective agonist G-1 promotes coupling to G??s and G??i proteins, resulting in adenylyl cyclase-mediated cAMP production and cytosolic calcium mobilization. Concurrently, GPER1 transactivates EGFR through Src and matrix metalloproteinase-dependent mechanisms, triggering phosphorylation of MAPK1/3 (ERK1/2) and AKT1. These effectors integrate estrogenic inputs into the MAPK/ERK and PI3K/Akt pathways, while interactions with ??-arrestin and G?¦? further diversify signaling outputs. In cancer contexts, this network drives proliferation, migration, and survival, and is modulated by agents such as tamoxifen.
In the VHL-deficient 786-O model, GPER1 knockout allows researchers to parse the contributions of estrogen-mediated rapid signaling to renal tumor biology. This system facilitates exploration of how GPER1 intersects with hypoxia-driven oncogenic pathways, influencing processes like cell growth and invasion. It serves as a valuable platform for assessing the role of sex hormones in clear cell RCC progression and for evaluating the efficacy of endocrine-targeted interventions.
Common experimental applications include western blotting and RT-qPCR for expression analysis, immunofluorescence for protein localization, and functional assays such as cell proliferation and transwell migration. Estrogen-induced phospho-ERK detection directly monitors GPER1 pathway activity, while RNA-seq enables transcriptome-wide profiling. Drug sensitivity assays can be used to test responses to tamoxifen and GPER1-selective compounds. For additional details, qualification data, or ordering information, please contact Ascent Research.
