The DNPH1 Knockout HGC-27 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HGC-27 human gastric adenocarcinoma cell line. This product consists of a heterogeneous pool of cells with disrupted DNPH1 genes, offering a loss-of-function model for studying nucleotide metabolism and oncogenic signaling without clonal biases.
HGC-27 is an epithelial cell line isolated from a lymph node metastasis of undifferentiated gastric adenocarcinoma. It is a standard model for gastric cancer research, exhibiting rapid proliferation and tumorigenic properties, and harboring genomic aberrations typical of gastric malignancies.
DNPH1 encodes a 2′-deoxynucleoside 5′-phosphate N-hydrolase that cleaves deoxynucleoside monophosphates, directly regulating dNTP pools critical for DNA replication and repair. Transcriptionally activated by c-Myc, DNPH1 functions downstream of this oncogenic transcription factor, interfacing with ribonucleotide reductase and the DNA damage response pathway monitored by p53. Knockout of DNPH1 disrupts nucleotide homeostasis, potentially leading to dNTP imbalances, replication stress, and cell cycle checkpoint activation.
In HGC-27 gastric cancer cells, DNPH1 disruption perturbs the c-Myc?CDNPH1?Cnucleotide metabolism axis, impairing the balance of nucleotide precursors necessary for sustained proliferation. This model is particularly relevant for studying how gastric cancer cells cope with replication stress and genomic instability, and for identifying synthetic lethal interactions with chemotherapeutics.
Applications include investigating c-Myc-driven oncogenesis, nucleotide metabolism in cancer, and drug sensitivity to nucleoside analogs like 5-fluorouracil. Typical assays comprise immunoblotting and RT-qPCR for DNPH1 expression, cell proliferation assays, ??H2AX immunofluorescence for DNA damage, LC-MS nucleotide pool analysis, and cell cycle flow cytometry. The cells also facilitate DNA damage response studies. For further information, contact Ascent Research.
