The APP Knockout 769-P Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the amyloid precursor protein (APP) gene. Produced from the 769-P host cell line, this product offers a mixed population of edited cells for studying APP loss of function in a human renal carcinoma context. This model is optimized for applications in cancer biology, neurobiology, and signal transduction research.
The 769-P line (ATCC CRL-1933) is an immortalized human clear cell renal cell adenocarcinoma cell line, derived from a primary tumor. It maintains epithelial morphology and tumorigenic properties, making it a standard platform for investigating kidney cancer proliferation, invasion, and therapeutic sensitivity. The APP knockout variant extends the utility of this line to dissect APP-dependent pathways in renal carcinoma.
APP is a type I transmembrane glycoprotein that functions as a cell surface receptor and adhesion molecule. Its proteolysis by BACE1 and ??-secretase (PSEN1/2) generates A??40/A??42 peptides and the AICD intracellular domain, which can transcriptionally regulate targets like NEP and GSK3B. APP assembles multimolecular complexes with adaptors FE65, Tip60, Shc, and Grb2, and directly binds integrin ??1 (ITGB1) to modulate adhesion and migration. It activates MAPK/ERK signaling via MAPK1/3 and PI3K/Akt via AKT1, integrating extracellular cues. APP expression is governed by upstream factors including NGF, retinoic acid, TGFB1, and IL1B.
In 769-P clear cell renal cell carcinoma, APP overexpression is linked to enhanced proliferation and tumorigenic potential, driven largely through ERK and PI3K/Akt cascades. The polyclonal APP knockout cell population provides a physiologically relevant tool to interrogate these mechanisms, enabling assessment of how APP loss impacts downstream effectors such as MAPK1 and AKT1. This model is particularly valuable for exploring the contribution of APP to renal cancer cell adhesion, invasion, and resistance to apoptosis.
Key research applications include Alzheimer??s disease modeling via secretase inhibitor evaluation (using A??40/42 ELISA), renal carcinoma proliferation and migration studies (MTT/CCK-8, wound healing, transwell assays), and molecular profiling through Western blotting of APP fragments, RT-qPCR for APP and BACE1, and immunofluorescence. Interactome studies by co-immunoprecipitation can probe associations with PSEN1, APLP1/2, FE65, and ITGB1, while RNA-seq reveals AICD-dependent transcriptional changes. Additionally, the model supports investigation of integrin-mediated adhesion crosstalk. For further details, please contact Ascent Research.
