The CD38 Knockout 769-P Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the 769-P human renal epithelial carcinoma cell line, engineered for loss-of-function studies of the CD38 gene. This product provides a heterogeneous pool of cells carrying targeted disruptions of CD38, enabling functional interpretation without clonal selection artifacts. The knockout model is designed to ablate CD38 expression, facilitating investigation of its enzymatic and receptor-mediated roles in cellular signaling and tumor biology.
The parental 769-P cell line originates from a primary clear cell renal cell carcinoma, a common subtype of kidney cancer. These cells exhibit characteristic VHL tumor suppressor gene mutation and consequent dysregulation of the hypoxia response pathway, including stabilization of hypoxia-inducible factor 1-alpha (HIF-1??) under normoxic conditions. This genetic background makes 769-P a relevant model for studying renal carcinoma metabolism, angiogenesis, and therapeutic resistance mechanisms.
CD38 encodes a multifunctional protein that functions as a cyclic ADP-ribose (cADPR) hydrolase and NAD+ glycohydrolase, and also acts as a receptor mediating adhesion and signal transduction. CD38 enzymatic activity converts NAD+ into cADPR and ADP-ribose, with cADPR serving as a potent second messenger that mobilizes intracellular calcium stores by activating ryanodine receptors on the endoplasmic reticulum. This calcium release triggers downstream signaling cascades including calcium/calmodulin-dependent protein kinase II (CaMKII), extracellular signal-regulated kinase (ERK), and protein kinase B (AKT). CD38 expression is regulated by factors such as retinoic acid, interferon-gamma (IFN-??), tumor necrosis factor-alpha (TNF-??), and HIF-1??, and it interacts with cell surface molecules including CD31/PECAM-1 and caveolin-1, linking it to adhesion and microenvironmental communication.
In the context of renal cell carcinoma, CD38 may contribute to tumor progression by modulating calcium-dependent proliferation and survival pathways, as well as influencing the tumor microenvironment through its receptor functions. The 769-P knockout model allows dissection of CD38??s role in metabolic adaptation, redox balance, and hypoxia-driven signaling, particularly given the cell line??s VHL mutation and HIF-1?? dysregulation. Disruption of CD38 permits evaluation of its impact on intracellular calcium oscillations, cAMP-mediated signaling, and purinergic signaling, which are often altered in cancer.
This polyclonal knockout cell product is suited for a wide array of research applications, including functional analysis of CD38 in renal carcinoma metabolism, investigation of calcium signaling dynamics using fluorescent indicators, and study of immune checkpoint molecule interactions. Researchers can employ assays such as Western blotting for protein expression verification, flow cytometry to assess surface receptor levels, NAD+ hydrolase activity measurements, cell proliferation and apoptosis assays, migration/invasion studies, RNA-seq transcriptome profiling, and drug sensitivity screening to explore resistance mechanisms. The heterogeneous nature of the polyclonal population also supports tumor microenvironment modeling and heterogeneity studies. For further technical details and ordering information, please contact Ascent Research.
