The AR Knockout 786-O polyclonal cells are a population of the human renal cell carcinoma line 786-O engineered with CRISPR/Cas9-mediated disruption of the androgen receptor (AR) gene. This polyclonal knockout model provides a heterogeneous loss-of-function system for investigating AR biology in a clear cell renal cancer context.
The host cell line, 786-O, is derived from a clear cell renal cell carcinoma (ccRCC) and harbors a VHL mutation. It is widely employed as an in vitro model for renal cancer, typically cultured in RPMI-1640 or DMEM, and retains key features of the disease, making it suitable for functional genomics and drug response studies.
Androgen receptor is a steroid hormone receptor and transcription factor activated by androgens such as testosterone. In the absence of ligand, AR resides in a cytoplasmic complex with HSP90 and FKBP52. Hormone binding promotes dissociation, dimerization, and nuclear translocation, where AR interacts with FOXA1, coactivators SRC-1/NCOA1 and SRC-2/NCOA2, and the SWI/SNF complex to bind androgen response elements (AREs) and drive expression of target genes, including KLK3, TMPRSS2, NKX3-1, FKBP5, and CCND1. Negative regulation is exerted by corepressors NCoR1 and SMRT/NCOR2. AR activity is further modulated by upstream regulators such as growth factors (EGF, IGF-1), IL-6, Src kinase, AKT, and MAPK1/3, linking AR to MAPK/ERK and PI3K/AKT/mTOR cascades.
In 786-O cells, AR knockout abrogates androgen-responsive transcription, impairing the regulation of genes involved in proliferation and survival. This polyclonal population allows the study of heterogeneous AR loss on renal carcinoma cell behavior, circumventing clonal artifacts. The VHL-mutant background provides a relevant platform to explore potential crosstalk between AR and hypoxia-related pathways.
This product supports diverse research applications, including mechanistic studies of AR in ccRCC, screening of AR-targeted therapies, and investigation of androgen signaling outside the prostate. Typical assays include ARE-driven luciferase reporters, ChIP-qPCR for AR binding, RT-qPCR for downstream targets, and phenotype-based assays such as MTT proliferation, colony formation, and migration/invasion. The polyclonal format facilitates robust experimental replicates. For additional information, please contact Ascent Research.
