The CASP6 Knockout MCF-7 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the MCF-7 human breast adenocarcinoma line, featuring targeted disruption of the CASP6 gene. This loss-of-function model provides a robust tool for dissecting the roles of executioner caspase-6 in apoptosis regulation, stress responses, and associated pathological conditions. The polyclonal format maintains genetic heterogeneity, minimizing clonal artifacts and enhancing representation of diverse editing events across the population.
The MCF-7 host cell line is an estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), luminal A breast cancer model originally isolated from a pleural effusion of a metastatic breast adenocarcinoma. These adherent epithelial cells retain functional p53 and are responsive to estrogens, making them a cornerstone for studying hormone-dependent tumor biology, endocrine therapy resistance, and apoptosis mechanisms in breast cancer.
Caspase-6, encoded by CASP6, is an executioner cysteine protease activated by upstream initiator caspases, including caspase-8 in the extrinsic pathway and caspase-9 in the intrinsic pathway, following stimulation by Fas ligand/TNF-alpha or cytochrome c/Apaf-1, respectively. Upon activation, caspase-6 cleaves critical substrates such as lamin A/C, PARP1, alpha-fodrin, tau, APP, and cytokeratin 18, thereby dismantling nuclear lamina, inactivating DNA repair, and promoting apoptotic morphological changes. Its activity is modulated by inhibitor of apoptosis proteins XIAP and survivin, and it operates within a cascading network involving caspase-3 and the apoptosome.
In MCF-7 cells, CASP6 knockout disrupts the execution phase of apoptosis, potentially leading to resistance against chemotherapeutic agents and inflammatory cytokines. This model is particularly valuable for investigating breast cancer cell survival mechanisms, as MCF-7 cells are widely used in studies of drug-induced apoptosis and the development of therapeutic resistance. The loss of caspase-6 function may also alter responses to genotoxic stress and modulate signaling pathways relevant to tumor progression, offering a platform to explore novel pro-apoptotic strategies.
This polyclonal knockout cell product is ideally suited for apoptosis research, chemoresistance testing, neurodegeneration modeling (given caspase-6’s role in cleaving tau and APP), anti-cancer drug screening, and inflammatory response studies. Representative assays include Western blotting for caspase-6 and its substrates (lamin A/C, PARP1), RT-qPCR, cell viability assays (MTT), flow cytometry using annexin V/PI staining, caspase activity measurements, immunofluorescence for nuclear fragmentation, and wound healing assays. For detailed information or ordering, please contact Ascent Research.
