The BTK Knockout 769-P Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population with targeted disruption of the Bruton??s tyrosine kinase (BTK) gene in the 769-P human clear cell renal cell carcinoma cell line. This model provides a genetically stable loss-of-function system for investigating BTK-dependent signaling in a VHL-mutant renal epithelial carcinoma background. The polyclonal format reflects a mixed population of edited cells, suitable for pooled functional analyses without subcloning bias.
The parental 769-P cell line is derived from a human clear cell renal cell carcinoma and carries a VHL mutation, a hallmark of the majority of sporadic clear cell renal carcinomas. These cells retain epithelial characteristics and are widely used as a model for renal cell carcinoma biology, including studies of hypoxic signaling, tumor metabolism, and cell migration. The VHL-deficient background offers a relevant context for exploring crosstalk between tumor suppressor loss and kinase signaling pathways.
BTK is a cytoplasmic non-receptor tyrosine kinase that is activated downstream of BCR engagement by Src family kinases LYN and SYK, and it is also recruited to the membrane by PI3K-generated PIP3. Once activated, BTK phosphorylates PLC??2 via the adaptor BLNK/SLP-65, initiating IP3/DAG-mediated Ca2? flux and NF-??B signaling. Additional downstream targets include ERK, AKT, and BTK autophosphorylation at Y223. While central to B cell development and immune responses, BTK signaling has been implicated in solid tumors, where it may modulate PLC??2-dependent proliferation and survival pathways.
In the 769-P renal carcinoma model, BTK knockout eliminates BCR-independent BTK functions, allowing examination of its role in solid tumor signaling. Loss of BTK may impair PLC??2 activation and NF-??B transcriptional programs, potentially affecting proliferation and survival. This model complements studies in B cell malignancies such as chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstr?m macroglobulinemia, and provides a tool to explore BTK’s contribution to VHL-mutant renal cancer pathobiology.
This polyclonal knockout population supports a variety of assays, including Western blotting for BTK and phospho-BTK (Y223), RT-qPCR for BTK and downstream targets, cell viability assays with BTK inhibitors, phospho-PLC??2 ELISA, and NF-??B reporter assays. Applications range from BTK inhibitor screening to dissecting BCR-related signaling in solid tumors and studying tumor-immune interactions. For additional information, contact Ascent Research.
