The IL1R1 Knockout PaTu 8988t Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the human IL1R1 gene. This product provides a heterogeneous pool of edited cells for loss-of-function studies of the type I IL-1 receptor. IL1R1 mediates pro-inflammatory responses to IL-1?? and IL-1??, principally through NF-??B and MAPK pathways. Disruption of IL1R1 abrogates these signaling cascades, enabling investigation of IL-1-dependent processes in a pancreatic cancer context.
The PaTu 8988t host cell line is a human pancreatic ductal adenocarcinoma derivative from a liver metastasis, carrying an activating KRAS mutation and exhibiting epithelial morphology. This line is extensively used to model metastatic behavior, invasion, and drug resistance in pancreatic cancer. Its metastatic origin and KRAS status make it a valuable system for studying tumor progression and therapeutic response.
IL1R1 is activated by IL-1?? or IL-1??, and antagonized by IL-1Ra. Ligand binding induces heterodimerization with the co-receptor IL1RAP, recruiting MyD88 and the kinases IRAK1/4. These activate TRAF6, which stimulates TAK1, leading to IKK-mediated NF-??B activation and JNK/p38 MAPK signaling. Downstream, NF-??B drives transcription of pro-inflammatory genes such as IL6, IL8/CXCL8, COX2, and MMPs. This positions IL1R1 upstream of key inflammatory circuits.
In the context of KRAS-mutant pancreatic cancer, IL-1 signaling promotes an inflammatory tumor microenvironment that enhances cell survival, invasion, and chemoresistance. By knocking out IL1R1 in PaTu 8988t cells, researchers can delineate the specific contributions of IL-1 to these malignant traits. The model offers a clean genetic background to study how loss of IL1R1 impacts tumor cell-intrinsic signaling and crosstalk with stromal elements.
These polyclonal knockout cells are suitable for assays including Western blot detection of phosphorylated I??B?? or NF-??B, quantification of IL-6/IL-8 secretion by ELISA, RT-qPCR of inflammatory transcripts, Transwell migration/invasion studies, and drug sensitivity testing (e.g., gemcitabine). NF-??B reporter assays and immunofluorescence for p65 nuclear translocation provide additional readouts. This reagent supports functional genomics, drug target validation, and studies of inflammation-driven tumor progression. For further information, please contact Ascent Research.
