DRAM2 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the human DRAM2 gene in the NCI-H1975 cell line. Generated via CRISPR/Cas9-mediated gene disruption, this product provides a loss-of-function model for studying DRAM2 biology. The polyclonal format reflects a mixed population of edited cells, suitable for pooled functional assays without clonal selection.
NCI-H1975 is a human lung adenocarcinoma cell line derived from non-small cell lung cancer (NSCLC). It harbors activating mutations in EGFR (epidermal growth factor receptor) and PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), which drive oncogenic signaling through the MAPK/ERK and PI3K/AKT pathways. This genetic background makes it a relevant model for NSCLC research, particularly in the context of autophagy and apoptosis regulation.
DRAM2 (DNA damage-regulated autophagy modulator 2) is a lysosomal protein and direct transcriptional target of the tumor suppressor p53 (TP53). Upon DNA damage, p53 induces DRAM2 expression, which promotes both autophagy and apoptosis. Mechanistically, DRAM2 functions upstream of the intrinsic apoptotic pathway: it interacts with BCL2 family proteins BAX and BAK, leading to cytochrome c release and caspase cascade activation. Concurrently, DRAM2 facilitates autophagic flux through interactions with ATG5 and LC3. Thus, DRAM2 integrates p53 signaling to coordinate cell death and autophagy in response to genotoxic stress, including chemotherapeutic agents.
In the NCI-H1975 background, DRAM2 knockout impairs DNA damage-induced apoptosis and autophagy, potentially contributing to tumor cell survival. Given that NCI-H1975 cells carry EGFR and PIK3CA mutations that sustain pro-survival signaling, disruption of DRAM2 may further attenuate cell death pathways, mimicking a common resistance mechanism in NSCLC. This model enables investigation of how loss of DRAM2-mediated autophagy and apoptosis affects cancer cell fitness, drug sensitivity, and the balance between mTOR and p53 signaling in a clinically relevant setting.
Researchers can employ DRAM2 Knockout NCI-H1975 Polyclonal Cells to explore autophagy dynamics via western blotting for LC3 lipidation and p62 degradation, or immunofluorescence for autophagosome puncta. Apoptosis studies using caspase-3/7 activity assays and clonogenic survival following DNA-damaging treatments (e.g., etoposide, cisplatin) are readily performed. The polyclonal population is suited for RT-qPCR confirmation of DRAM2 disruption and for high-throughput drug sensitivity screens targeting EGFR or PI3K pathways. This knockout model serves as a valuable tool for dissecting p53-DRAM2 axis function in NSCLC and identifying synthetic lethal interactions. For further details or technical support, please contact Ascent Research.
