The TNFRSF10B Knockout MIA PaCa-2 Cell Line is a genetically engineered human pancreatic adenocarcinoma cell product in which the TNFRSF10B gene has been disrupted using CRISPR/Cas9-mediated genome editing. This knockout cell line is derived from the MIA PaCa-2 parental line and provides a stable loss-of-function model for studying death receptor 5 (DR5) biology. The product is supplied as a ready-to-use cell line with confirmed target gene disruption, suitable for a wide range of functional and mechanistic studies in apoptosis and cancer research.
MIA PaCa-2 is a well-characterized human pancreatic adenocarcinoma cell line harboring a KRAS G12C activating mutation, representing a clinically relevant model for pancreatic ductal adenocarcinoma (PDAC). These cells exhibit features of epithelial origin and are widely used to investigate tumor cell signaling, drug resistance, and apoptotic pathways. The line is adherent and exhibits robust growth in standard culture conditions, facilitating reproducible experimental setups. The KRAS G12C background makes this line particularly valuable for exploring oncogene-driven survival mechanisms and their intersection with death receptor signaling.
TNFRSF10B encodes DR5, a transmembrane death receptor of the tumor necrosis factor receptor superfamily that serves as the primary signaling-competent receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Upon TRAIL binding, DR5 recruits the adaptor protein FADD and initiator caspase-8 to form the death-inducing signaling complex (DISC), triggering activation of caspase-8 and subsequent cleavage of effector caspase-3 and Bid. This cascade can engage the mitochondrial amplification loop through cytochrome c release, Apaf-1, and caspase-9, leading to robust extrinsic apoptosis. In addition, DR5 signaling can activate non-apoptotic outputs through NF-??B and JNK pathways, mediated by RIPK1 and other downstream effectors. Upstream regulators of DR5 expression include the tumor suppressor p53 and DNA damage responses, making DR5 a nexus for both extrinsic and intrinsic death signals. Decoy receptors DcR1 and DcR2 compete with DR5 for TRAIL binding, adding a layer of regulatory control.
In the MIA PaCa-2 pancreatic cancer model, knockout of TNFRSF10B ablates the primary TRAIL receptor, rendering cells resistant to TRAIL-induced apoptosis. This deficiency provides a clean genetic tool to dissect mechanisms of apoptosis evasion and to evaluate strategies that re-sensitize cancer cells to death receptor-mediated killing. Given the KRAS G12C driver mutation, this knockout line is particularly useful for studying how oncogenic signaling intersects with the extrinsic apoptotic machinery and for testing whether targeted therapies can restore DR5-independent apoptotic programs.
Typical research applications of the TNFRSF10B Knockout MIA PaCa-2 Cell Line include investigation of TRAIL resistance mechanisms, screening of DR5 agonists or apoptosis sensitizers, and analysis of compensatory survival pathways in pancreatic cancer. The line is suitable for a variety of experimental readouts such as caspase activity assays, Annexin V/PI flow cytometry for apoptosis quantification, MTT or colony formation viability assays, and Western blotting or RT-qPCR for pathway component expression. It also supports combination therapy studies to evaluate synergy between death receptor activators and other agents. For further technical details and ordering information, please contact Ascent Research.
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