The BCL2 Knockout 769-P Polyclonal Cells constitute a CRISPR/Cas9-mediated gene disruption model in which the BCL2 locus has been targeted to generate a polyclonal knockout cell population derived from the human 769-P renal cell carcinoma line. This product provides a heterogeneous pool of edited cells with loss-of-function mutations, enabling the study of BCL2-dependent processes without clonal selection bias.
The 769-P cell line is an established model of clear cell renal cell carcinoma (ccRCC), originally derived from a primary tumor and characterized by an epithelial morphology. Notably, 769-P cells retain wild-type VHL, distinguishing them from the majority of ccRCC lines that harbor VHL mutations, and thus representing a unique platform for investigating VHL-independent apoptotic regulation and tumorigenesis.
BCL2 is a central anti-apoptotic protein that localizes to the mitochondrial outer membrane, where it binds and sequesters the pro-apoptotic effectors BAX and BAK, preventing mitochondrial outer membrane permeabilization (MOMP) and cytochrome c release. Its anti-apoptotic activity is antagonized by BH3-only proteins, including BIM, PUMA, and NOXA, which displace BAX/BAK or promote their activation. BCL2 expression is regulated by p53-mediated repression via miR-15a/16-1 and by PI3K/AKT/NF-??B-dependent induction, as well as by cytokine signals such as IL-3 and GM-CSF. BCL2 also binds BECLIN1 to inhibit autophagy, further contributing to cell survival.
In the 769-P ccRCC context, disruption of BCL2 removes a critical anti-apoptotic checkpoint, rendering cells more susceptible to intrinsic apoptosis triggered by cellular stress or chemotherapeutic agents. Given that renal cell carcinoma frequently exhibits resistance to conventional therapies through aberrant apoptosis regulation, this knockout model offers a relevant tool to dissect BCL2-mediated survival mechanisms and to evaluate the role of BCL2 in tumor maintenance independently of VHL status.
This cell model supports a broad range of experimental applications, including quantitative analysis of apoptosis signaling by Annexin V staining, caspase-3/7 activity assays, cytochrome c release measurement, and mitochondrial membrane potential assessment using JC-1 dye. It is well-suited for screening BH3 mimetics such as venetoclax, thereby facilitating drug discovery efforts targeting BCL2-dependent cancers. Additional applications include xenograft tumorigenicity studies to assess the impact of BCL2 loss on in vivo tumor growth, as well as molecular profiling via western blotting and RT-qPCR. For further details or to request a quote, please contact Ascent Research.
