The HSP90AB1 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human renal epithelial carcinoma line 786-O, with targeted disruption of the HSP90AB1 gene. This loss-of-function model, generated via CRISPR/Cas9-mediated gene disruption, provides a heterogeneous cell pool that avoids single-cell clonal selection, more closely mimicking the genetic diversity found in tumor populations. The product is designed for functional studies requiring HSP90AB1 ablation without isolation of monoclonal clones.
The parental 786-O cell line originates from a primary clear cell adenocarcinoma of the kidney, serving as a widely used in vitro model of clear cell renal cell carcinoma (ccRCC). These cells bear a VHL mutation that constitutively stabilizes HIF transcription factors, driving a pseudohypoxic gene expression program. This genetic background is instrumental for investigating signaling networks central to ccRCC, including those mediated by HIF1A, mTOR, and receptor tyrosine kinases, and supports dissection of tumor cell proliferation, migration, and drug response.
HSP90AB1 encodes the ATP-dependent molecular chaperone HSP90AB1, which maintains the stability and activity of a diverse array of client proteins, including kinases (AKT, EGFR, HER2, CDK4), transcription factors (HIF1A, steroid hormone receptors), and signaling intermediates. Its chaperone cycle is regulated by co-chaperones such as CDC37, p23, AHA1, HSP70, and HOP, and its expression is induced by HSF1 under heat shock or growth factor stimulation. Through these clients, HSP90AB1 integrates into PI3K/AKT/mTOR, MAPK/ERK, and JAK/STAT pathways, modulating cell growth, survival, and stress adaptation.
In the context of 786-O ccRCC cells, HSP90AB1 is critical for oncogenic signaling. Knockout of HSP90AB1 is expected to destabilize key clients like HIF1A, AKT, and ERK, thereby disrupting the pseudohypoxic and proliferative drivers of tumorigenesis. The resulting loss of chaperone function leads to proteasomal degradation of these proteins, impairing downstream signaling and potentially reducing cell viability, inducing apoptosis, and attenuating invasive capacity. This model offers a platform to probe HSP90AB1 dependency and identify compensatory mechanisms in renal carcinoma.
These polyclonal knockout cells are suited for a range of applications, including western blotting and co-immunoprecipitation to assess client protein levels and complex formation. Functional assays such as cell viability (e.g., MTT), apoptosis (Annexin V staining), and migration/invasion (Transwell) can quantify phenotypic changes upon HSP90AB1 loss. Additionally, drug sensitivity studies with HSP90 inhibitors (e.g., geldanamycin derivatives) compared between knockout and parental cells can elucidate resistance pathways and synthetic lethal interactions. For further details or technical assistance, please contact Ascent Research.
