The HRH1 Knockout PaTu 8988t Polyclonal Cells comprise a polyclonal population of Homo sapiens PaTu 8988t cells engineered via CRISPR/Cas9-mediated disruption of the HRH1 gene, which encodes the histamine H1 receptor. This product provides a loss-of-function model for studying HRH1-dependent signaling in a pancreatic ductal adenocarcinoma (PDAC) context. The polyclonal format ensures a heterogeneous pool of edited alleles, facilitating pooled loss-of-function studies without clonal bias.
The host cell line PaTu 8988t is a widely used in vitro model derived from a primary human pancreatic ductal adenocarcinoma. This line retains key features of PDAC, including characteristic genetic alterations and phenotypic traits, making it suitable for investigating molecular mechanisms of pancreatic cancer progression, metastasis, and therapeutic response. PaTu 8988t cells are particularly valued for their ability to recapitulate aspects of tumor biology in a controlled experimental setting.
HRH1 encodes the histamine H1 receptor, a Gq/11-coupled GPCR. Upon histamine binding, the receptor activates Gq/11 proteins (GNA11), which stimulate phospholipase C beta (PLCB2) to hydrolyze PIP2 into inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 triggers calcium release from intracellular stores via ITPR channels, while DAG activates protein kinase C (PRKCA). These second messengers converge on mitogen-activated protein kinase (MAPK3/ERK1/2) and nuclear factor kappa B (NFKB1) pathways, leading to transcriptional regulation via AP-1 and other factors. The receptor is also modulated by beta-arrestin and GRK2-mediated desensitization. Upstream, HRH1 transcription is augmented by IL-4 and IL-13, linking it to inflammatory cascades.
In pancreatic cancer, aberrant histamine signaling via HRH1 has been implicated in modulating tumor cell proliferation, migration, and interactions with the tumor microenvironment. By disrupting HRH1 in PaTu 8988t cells, this knockout model enables dissection of histamine-driven effects on PDAC pathophysiology. Researchers can assess changes in calcium dynamics, MAPK/NF-kB activity, and cellular behaviors, providing insights into the receptor’s contribution to pancreatic cancer aggressiveness and its potential as a therapeutic target.
This polyclonal knockout product is suited for a range of functional studies, including histamine stimulation assays coupled with phospho-ERK detection by Western blotting, calcium flux measurements, and NF-kB reporter assays. It also supports cell proliferation (MTT), migration (transwell), and gene expression analyses via RT-qPCR. Applications span target validation in allergic and inflammatory disorders, exploration of HRH1??s role in tumor progression, and pharmacological profiling of H1 receptor antagonists. For detailed experimental protocols or technical support, please contact Ascent Research.
