The DNPEP Knockout NCI-H1299 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1299 human non-small cell lung carcinoma (NSCLC) epithelial cell line. This loss-of-function model targets the aspartyl aminopeptidase (DNPEP) gene, facilitating studies of its role in peptide hormone processing and protein turnover. The polyclonal nature avoids clonal bias, providing a genetically diverse pool with disrupted DNPEP expression.
The host cell line, NCI-H1299, was derived from a lymph node metastasis of a 43-year-old Caucasian male with lung carcinoma. This p53-deficient, KRAS wild-type NSCLC epithelial line is widely employed in studies of metastasis, tumorigenicity, and drug responsiveness, providing a robust and well-characterized platform for cancer biology research.
DNPEP is a cytosolic aspartyl aminopeptidase that specifically removes N-terminal aspartate from peptides, critically regulating the renin-angiotensin system (RAS). It converts angiotensin I to angiotensin III and angiotensin II to angiotensin IV, thereby modulating signaling through AT1R and AT2R receptors. Upstream, DNPEP expression is controlled by transcription factors such as SP1 and AP-1, and its activity is influenced by substrate availability and angiotensin II levels. DNPEP forms homodimers and interacts with other aminopeptidases (LAP3, NPEPPS) and proteasome components, linking it to protein degradation and antigen processing. Downstream effects include altered processing of antigenic peptides and fine-tuning of angiotensin-mediated pathways.
In NCI-H1299 cells, DNPEP knockout is expected to disrupt the balance of angiotensin peptides, potentially affecting AT1R/AT2R-mediated cell proliferation, migration, and invasion. Given the role of RAS in tumor microenvironments, loss of DNPEP may impair peptide hormone processing and alter the antigenic peptide repertoire, impacting immune recognition and cancer cell behavior. This model serves as a unique tool to dissect the contribution of aspartyl aminopeptidase activity to lung adenocarcinoma progression and to evaluate downstream oncogenic signaling networks in a metastasis-derived context.
This knockout model supports a broad range of studies, including lung cancer biology, RAS pathway analysis, peptide hormone signaling, functional genomics, and drug target validation. Compatible assays encompass western blotting, RT-qPCR, angiotensin peptide ELISA or mass spectrometry, migration/invasion assays, proliferation assays, and transcriptomic analyses such as RNA-seq. By enabling systematic investigation of DNPEP-dependent mechanisms, these polyclonal knockout cells facilitate discovery and validation in cancer research. For additional information, please contact Ascent Research.
