The HMOX1 Knockout 769-P Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the 769-P human renal cell carcinoma line, with targeted disruption of the HMOX1 gene encoding heme oxygenase-1 (HO-1). This polyclonal knockout model eliminates HO-1 expression in a genetically heterogeneous pool, enabling functional studies without clonal selection biases.
The 769-P parental line was established from a primary clear cell adenocarcinoma of the kidney and exhibits features of renal proximal tubule epithelial cells. This widely used RCC model provides a relevant background for investigating the interplay between heme metabolism, oxidative stress, and cancer cell survival.
HO-1 is a stress-inducible enzyme that degrades heme into biliverdin, carbon monoxide (CO), and Fe2?. Biliverdin is reduced to the antioxidant bilirubin by biliverdin reductase, CO activates guanylyl cyclase/cGMP signaling, and Fe2? promotes ferritin synthesis. HMOX1 expression is regulated by transcription factors Nrf2, Bach1, and HIF-1??, and induced by heme, heat shock, heavy metals, and cytokines such as IL-10 and IL-6. HO-1 interacts with NADPH-cytochrome P450 reductase and Keap1, and its activity influences downstream targets including p21 and VEGF. Knockout of HMOX1 in 769-P cells abrogates heme degradation, leading to elevated oxidative stress, loss of CO and bilirubin cytoprotection, and potential sensitization to ferroptosis or apoptosis.
In 769-P renal cancer cells, HO-1 upregulation contributes to chemoresistance and redox homeostasis. HMOX1 disruption in this polyclonal population impairs antioxidant defenses, enhancing susceptibility to oxidative insults such as cisplatin or lipid peroxidation. This model enables the study of heterogeneous stress responses and selection dynamics, providing a realistic platform to explore HO-1??s role in tumor biology.
Applications include investigating ferroptosis via ROS and lipid peroxidation assays, assessing drug sensitivity under oxidative stress, and probing Nrf2-mediated signaling. Common validation methods include western blot, RT-qPCR, heme oxygenase activity assays, bilirubin/CO detection, and Nrf2 translocation studies. This knockout model is a valuable tool for research on renal cancer, redox regulation, and cytoprotective mechanisms. For additional information, please contact Ascent Research.
