TP53 Knockout PC-9 Cell Line

The TP53 Knockout PC-9 Cell Line is a CRISPR/Cas9-edited knockout model with targeted disruption of the TP53 gene in PC-9 human lung adenocarcinoma cells. This cell line serves as a loss-of-function tool for studying p53-dependent tumor suppression mechanisms, supplied as a stable and ready-to-use resource for genetic and pharmacological investigations.

The parental PC-9 cell line, derived from non-small cell lung cancer (NSCLC), harbors an activating EGFR exon 19 deletion (delE746-A750), which drives sensitivity to EGFR tyrosine kinase inhibitors. Its epithelial origin and defined genetic background make it a widely employed model for lung cancer biology and targeted therapy research.

TP53 encodes the p53 transcription factor, a tumor suppressor activated by stress signals including DNA damage and oncogene activation. Upstream kinases ATM and ATR phosphorylate p53, while MDM2 promotes its degradation. Activated p53 transcriptionally regulates a network of targets: CDKN1A/p21 induces cell cycle arrest; BAX and PUMA drive apoptosis; GADD45A participates in DNA repair; and miR-34a modulates gene expression. Interacting cofactors like p300/CBP, ASPP1/2, and 14-3-3?? fine-tune p53 activity. Canonical pathways include ATM/ATR ?? CHK1/CHK2 ?? p53 ?? p21 ?? CyclinE/CDK2 and p53 ?? BAX/BAK ?? cytochrome c release ?? caspase activation.

In PC-9 cells, TP53 knockout eliminates p53-mediated tumor suppression, enabling evasion of apoptosis and senescence in response to DNA-damaging agents such as cisplatin and etoposide. The combination of EGFR mutation and p53 deficiency mirrors genetic profiles frequently observed in lung adenocarcinoma patients, making this knockout model valuable for analyzing cooperative oncogenic pathways, identifying synthetic lethality interactions, and assessing drug sensitivity in a p53-null background.

Researchers employ the TP53 Knockout PC-9 Cell Line in diverse workflows including drug sensitivity screens, apoptosis assays (Annexin V, caspase-3/7), cell cycle analysis (flow cytometry with propidium iodide staining), DNA damage response evaluation (??H2AX immunofluorescence), and transcriptomic profiling (RNA-seq). Western blotting for p53, p21, and BAX confirms knockout and downstream pathway dysregulation. These applications support oncology research, DNA damage signaling studies, tumor suppressor mechanism elucidation, and the development of therapeutic strategies for p53-deficient lung cancers. For ordering information or technical inquiries, please contact Ascent Research.