The ATF4 Knockout A2780 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human ovarian carcinoma cell line A2780, designed to disrupt the ATF4 gene. This polyclonal product provides a heterogeneous pool of cells carrying diverse loss-of-function alleles, enabling the study of conserved ATF4-dependent signaling events without clonal selection artifacts. The population is well-suited for experiments requiring robust genetic perturbation of the integrated stress response pathway.
A2780 is an epithelial ovarian cancer cell line established from an endometrioid adenocarcinoma, widely used as a model for high-grade serous carcinoma. A2780 cells retain sensitivity to platinum-based agents and activate cytoprotective stress pathways, making them an ideal host for investigating ATF4’s role in tumor cell survival and chemoresistance. The polyclonal knockout in this background allows examination of ATF4 functions within a clinically relevant ovarian cancer context.
ATF4 functions as a master transcription factor of the integrated stress response (ISR), activated downstream of eIF2?? phosphorylation by kinases including EIF2AK3 (PERK), EIF2AK4 (GCN2), EIF2AK2 (PKR), and EIF2AK1 (HRI) during ER stress, amino acid deprivation, and oxidative stress. Upon translation, ATF4 induces expression of target genes such as DDIT3 (CHOP), ATF3, PPP1R15A (GADD34), ASNS, SLC7A11, VEGFA, BCL2, and PMAIP1 (NOXA), thereby regulating amino acid metabolism, redox homeostasis, autophagy, and apoptosis. ATF4 also associates with transcriptional partners including CREBBP/EP300 (CBP/p300), CHOP, ATF3, and JUN to integrate upstream signals from mTORC1 and hypoxia. This network positions ATF4 as a central mediator of adaptive and apoptotic responses.
In ovarian carcinoma, ATF4-driven ISR contributes to cisplatin resistance by promoting pro-survival genes and modulating autophagic and apoptotic pathways. The A2780 ATF4 knockout polyclonal cells enable detailed dissection of how ATF4 loss alters sensitivity to ER stress inducers like tunicamycin, affects cell viability under nutrient deprivation, and reshapes downstream gene expression. This model is particularly valuable for exploring feedback mechanisms via GADD34-mediated eIF2?? dephosphorylation and for identifying ATF4-dependent vulnerabilities that could be exploited therapeutically.
Researchers can utilize this polyclonal knockout product for western blotting and RT-qPCR analyses of ATF4, phospho-eIF2??, CHOP, and ATF3; tunicamycin- or amino acid starvation-induced ISR assays; cell viability and apoptosis quantification under stress; and cisplatin dose-response curves to assess chemoresistance. Additional applications include immunofluorescence for ATF4 nuclear translocation, RNA-seq transcriptomic profiling to map ATF4 regulons, and phospho-eIF2?? flow cytometry to monitor ISR activation kinetics. For further technical details, please contact our support team.
