The CBR1 Knockout 786-O Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal cell population derived from the 786-O clear cell renal cell carcinoma line, in which the CBR1 gene has been disrupted by CRISPR/Cas9-mediated genome editing. This pooled knockout format provides a heterogeneous loss-of-function model that eliminates the need for single-cell cloning while maintaining the functional diversity of the engineered cell population. The product is designed for researchers investigating carbonyl reductase 1 biology and its roles in drug metabolism, chemoresistance, and prostaglandin regulation within a clinically relevant kidney cancer background.
The host cell line, 786-O, is a well-characterized clear cell renal cell carcinoma model isolated from a primary tumor of a 58-year-old male. These cells carry a naturally occurring mutation in the VHL tumor suppressor gene, leading to constitutive activation of hypoxia-inducible factor pathways and altered metabolic states typical of renal carcinoma. The VHL-deficient background makes 786-O an established system for studying tumor hypoxia, metabolic reprogramming, and the molecular basis of renal cell carcinoma progression.
CBR1 encodes an NADPH-dependent carbonyl reductase that catalyzes the reduction of a wide range of endogenous and xenobiotic carbonyl substrates, including prostaglandins, steroids, and anthracycline chemotherapeutics. CBR1 expression is transcriptionally regulated by NFE2L2 (Nrf2) and AHR, connecting oxidative stress and xenobiotic sensing to cellular detoxification networks. Downstream, CBR1 directly governs the metabolism of prostaglandin E2 and the inactivation of anthracyclines such as daunorubicin and doxorubicin, and it participates in lipid aldehyde reduction. Within the broader metabolic network, CBR1 operates in concert with PTGS2, PTGES, AKR1C3, and CYP3A4, integrating signals from arachidonic acid metabolism, steroid hormone processing, and drug detoxification pathways.
Disruption of CBR1 in the VHL-mutant 786-O background abrogates NADPH-dependent carbonyl reduction capacity, directly affecting prostaglandin metabolism and the detoxification of anthracycline drugs. This combination of VHL loss and CBR1 knockout creates a unique cellular context for examining the interplay between oncogenic signaling, redox homeostasis, and carbonyl stress responses. The model is particularly relevant for dissecting mechanisms of chemoresistance in renal cell carcinoma, where altered drug metabolism can influence therapeutic outcomes.
This polyclonal knockout cell product is well-suited for detailed investigation of carbonyl reductase function in cancer chemoresistance, including anthracycline sensitivity profiling through drug dose?Cresponse and flow cytometry-based apoptosis assays. Researchers can confirm target disruption by western blotting and RT-qPCR, quantify prostaglandin E2 levels to assess metabolic consequences, and measure NADPH consumption to monitor enzymatic activity directly. The cells also enable studies of Nrf2- and AHR-regulated detoxification pathways and the role of reactive carbonyl species in renal carcinoma progression. For additional information or technical assistance, please contact Ascent Research.
