EGFR Knockout HK-2 Cell Line

The EGFR Knockout HK-2 Cell Line is a CRISPR/Cas9-edited human knockout cell line with targeted disruption of the epidermal growth factor receptor (EGFR) gene. This loss-of-function model enables dissection of EGFR-mediated signaling in a physiologically relevant renal proximal tubule epithelial context. Delivered as an established cell line, it ensures reproducible genetic ablation of EGFR, facilitating studies on cell proliferation, survival, and differentiation without the confounding effects of transient gene silencing or pharmacological inhibitors.

The HK-2 cell line originates from normal human kidney proximal tubule epithelium and is immortalized to retain key functions such as reabsorption and secretion. With a normal genetic background and epithelial phenotype, HK-2 cells serve as a standard in vitro model for nephrotoxicity, renal physiology, and drug transport studies. The EGFR knockout in HK-2 provides a clean platform to investigate how EGFR loss alters proximal tubule cell behavior under both homeostatic and disease-mimicking conditions.

EGFR is a receptor tyrosine kinase activated by ligands including EGF, TGF-??, amphiregulin, and HB-EGF, leading to dimerization and autophosphorylation. This recruits adaptors Grb2 and Shc, which associate with Cbl and ErbB2 to trigger the MAPK/ERK cascade (GRB2, SOS, RAS, RAF, MEK, ERK) and the PI3K/AKT pathway (PI3K, AKT, mTOR). These pathways transcriptionally regulate c-Fos, c-Jun, MYC, and cyclin D1, thereby promoting proliferation, survival, and migration. Additionally, EGFR signals through JAK/STAT and PLC??/PKC. The knockout cell line ablates these signaling axes, allowing precise interrogation of ligand-receptor interactions and downstream effectors.

In the kidney, EGFR contributes to epithelial cell renewal and repair, but its aberrant activation drives polycystic kidney disease via cyst epithelial proliferation, renal fibrosis through matrix deposition, and acute kidney injury by modulating repair. The EGFR Knockout HK-2 Line enables dissection of these pathological mechanisms, offering insights into how EGFR loss affects cell cycle, apoptosis, or epithelial-mesenchymal transition in renal diseases, and serving as a platform to test EGFR-targeted therapies.

Applications encompass renal drug toxicity screening to uncover EGFR-mediated nephroprotection or injury; kidney disease modeling for polycystic kidney disease and fibrosis; EGFR signaling studies using techniques like western blotting, RT-qPCR, and phospho-ERK ELISA; and renal cancer research. Assays such as immunofluorescence, MTT, and wound healing further support functional analysis. For inquiries or service requests, contact Ascent Research.