ACSS2 Knockout MCF-7 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the MCF-7 human breast adenocarcinoma cell line, with targeted disruption of the ACSS2 gene. This loss-of-function model facilitates the study of ACSS2, an enzyme that converts acetate to acetyl-CoA, providing a key substrate for lipid synthesis and histone acetylation. The polyclonal nature preserves diverse genetic backgrounds, enabling robust functional analyses.
The MCF-7 parent line is an adherent epithelial cell model isolated from a pleural effusion of a 69-year-old female with metastatic mammary adenocarcinoma. These cells are estrogen receptor-positive, progesterone receptor-positive, and HER2-negative, representative of the luminal A breast cancer subtype. MCF-7 is widely employed to investigate hormone-dependent signaling, tumor metabolism, and therapeutic responses, and its well-defined metabolic characteristics make it an ideal system for studying acetyl-CoA metabolism.
ACSS2 converts acetate to acetyl-CoA, a metabolite essential for lipid synthesis, energy, and histone acetylation. Regulated by HIF-1?? and SREBP1 and interacting with AMPK and SIRT1, ACSS2-derived acetyl-CoA fuels FASN-mediated lipogenesis and p300/CBP-mediated histone acetylation. Under hypoxic or nutrient-deprived conditions, this acetate-dependent acetyl-CoA supply sustains anabolic and epigenetic processes critical for tumor cell proliferation.
In MCF-7 cells, ACSS2 is positioned to support metabolic reprogramming and epigenetic regulation. Estrogen receptor-positive breast cancer models rely on lipid metabolism for membrane synthesis and signaling, and ACSS2-mediated acetyl-CoA generation likely contributes to lipid droplet formation and oncogenic histone acetylation patterns. The HIF-1???CACSS2 axis is particularly relevant under tumor hypoxia, where acetate can compensate for reduced glucose-derived acetyl-CoA. Disrupting ACSS2 in this polyclonal model provides a platform to dissect these tumor-specific metabolic adaptations.
Applications include [13C]-acetate labeling and LC-MS metabolomics to track acetyl-CoA flux, lipid droplet staining to assess neutral lipid stores, and histone acetylation ChIP-qPCR to map epigenetic changes. Functional assays such as colony formation and proliferation analyses can evaluate the role of ACSS2 in tumorigenic capacity under normoxia and hypoxia. The model is also valuable for drug target validation and metabolic inhibitor studies. For further information, contact Ascent Research.
