The CCDC90B knockout NCI-H1975 polyclonal cells are a CRISPR/Cas9-edited cell population derived from the human non-small cell lung adenocarcinoma line NCI-H1975, featuring targeted disruption of the CCDC90B gene. As a polyclonal knockout model, this product provides a heterogeneous pool of edited alleles, retaining biological variability while eliminating CCDC90B protein expression in the majority of cells. It is designed for functional studies of apoptosis, drug resistance, and oncogenic signaling without the bottleneck of single-cell cloning.
The NCI-H1975 host cell line is a well-characterized model of lung adenocarcinoma that carries EGFR L858R and T790M mutations along with a PIK3CA mutation, conferring resistance to first-generation EGFR tyrosine kinase inhibitors and activating the PI3K/AKT pathway. This epithelial cell line, derived from a female patient, is extensively used to investigate mechanisms of acquired resistance to EGFR-targeted therapy and tumor progression in NSCLC.
CCDC90B encodes a pro-apoptotic mitochondrial protein that antagonizes anti-apoptotic BCL2 family members, including BCL2 and BCL2L1. Upon activation by p53 and cellular stress signals, CCDC90B localizes to mitochondria, interacts with BCL2/BCL2L1, and neutralizes their inhibition of BAX/BAK, thereby promoting mitochondrial outer membrane permeabilization. This leads to cytochrome c release, APAF1 apoptosome assembly, and sequential activation of caspase-9 and caspase-3, driving apoptotic execution. Thus, CCDC90B operates as a key mediator of the intrinsic apoptotic pathway downstream of DNA damage and p53.
In the NCI-H1975 background, dysregulation of apoptosis contributes to both tumorigenesis and chemoresistance. CCDC90B loss may cooperate with EGFR and PI3K oncogenic signals to impair mitochondrial apoptosis, making this knockout model valuable for dissecting the interplay between survival signaling and apoptotic blockade. It enables investigation of how CCDC90B deficiency influences sensitivity to chemotherapeutics, EGFR inhibitors, and emerging combination strategies in lung adenocarcinoma.
These polyclonal knockout cells support a broad array of assays for apoptosis and lung cancer research. Target disruption can be confirmed by RT-qPCR, while functional effects are assessable via western blotting for cleaved caspase-3 and PARP, caspase activity assays, and cytochrome c release immunofluorescence. Flow cytometry with annexin V/PI discriminates apoptotic and necrotic cells, and mitochondrial health can be probed using JC-1 potential measurements. Co-immunoprecipitation enables direct study of CCDC90B?CBCL2 interactions. In viability and drug-response assays, the cells facilitate screening for chemosensitizers or synthetic lethal partners. For more details or to order, please contact Ascent Research.
