The BACE2 Knockout SK-HEP-1 Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal knockout population derived from the human SK-HEP-1 hepatic adenocarcinoma cell line, providing a reliable loss-of-function model for functional studies. This product features targeted disruption of the BACE2 gene across a heterogeneous cell pool, preserving population-level diversity and minimizing clonal selection artifacts. The gene disruption enables investigation of BACE2 functions in amyloid precursor protein (APP) processing, insulin receptor signaling, and liver cancer biology.
SK-HEP-1 is a human hepatic adenocarcinoma cell line established from the ascitic fluid of a patient with adenocarcinoma, representing an epithelial liver tumor model. This line expresses insulin receptors and glucose transporters, and retains oncogenic signaling pathways characteristic of hepatocellular carcinoma. Its metabolic and proliferative features make it a robust system for studying hepatic cancer biology and insulin-related metabolic regulation.
BACE2 is a transmembrane aspartic protease that cleaves APP within the ??-amyloid region, preventing neurotoxic A?? formation and favoring the non-amyloidogenic processing pathway. It also processes PMEL for melanosome biogenesis and modulates insulin receptor (INSR) signaling. BACE2 expression is transcriptionally regulated by SP1, NF-??B, and factors responsive to hypoxia, glucose concentration, and insulin. The protease interacts directly with APP, PMEL, and INSR, and its activity influences downstream effectors including IRS1 and AKT phosphorylation, which control glucose metabolism and cell survival. Parallel pathways involve BACE1 and the ??-secretase complex (comprising PSEN1, PSEN2, NCSTN, APH-1, and PSENEN).
Knocking out BACE2 in SK-HEP-1 cells generates a physiologically relevant platform for dissecting its dual roles in hepatic insulin resistance and cancer cell behavior. Ablation disrupts APP cleavage profiles and insulin receptor processing, potentially altering proliferation, glucose uptake, and downstream AKT signaling. This model is particularly suited for assessing BACE2??s putative functions in hepatocellular carcinoma, where it may modulate tumor growth and metabolic adaptation. The liver epithelial context also allows study of BACE2??s impact on pathways shared with type 2 diabetes.
Routine applications encompass western blot and qRT-PCR for verifying BACE2 knockout, sAPP?? and A?? secretion assays, insulin receptor cleavage monitoring, cell proliferation and glucose uptake measurements, phospho-AKT analysis, transcriptomic profiling via RNA-seq, and flow cytometric assessment of surface receptor expression. This cell model advances research in Alzheimer??s disease, type 2 diabetes, hepatocellular carcinoma, BACE2 inhibitor development, ??-secretase substrate identification, and melanogenesis. For technical inquiries or protocol support, please contact Ascent Research.
