This product comprises a CRISPR/Cas9-edited polyclonal knockout cell population in which the HDAC1 gene has been disrupted in the PaTu 8988t human pancreatic ductal adenocarcinoma (PDAC) cell line. The polyclonal format provides a mixed population of edited cells, enabling robust loss-of-function studies without single-cell cloning bias. Disruption of HDAC1 by CRISPR/Cas9 yields a model system to interrogate the epigenetic and transcriptional roles of this class I histone deacetylase in a KRAS/TP53-mutant pancreatic cancer background.
The PaTu 8988t cell line originates from a liver metastasis of a pancreatic adenocarcinoma and carries oncogenic KRAS G12V and TP53 mutations, reflecting the genetic landscape of aggressive PDAC. These cells exhibit a transformed, pancreatic exocrine phenotype and are widely used to investigate molecular mechanisms of pancreatic tumorigenesis, metastasis, and therapeutic resistance. The genetic background of PaTu 8988t, with its well-characterized driver mutations, makes it a clinically relevant host for studying HDAC1-dependent pathways in pancreatic cancer progression.
HDAC1 is a histone deacetylase that catalyzes the removal of acetyl groups from lysine residues on histone H3 and H4 tails, leading to chromatin compaction and transcriptional silencing. Beyond histones, HDAC1 deacetylates non-histone substrates such as p53 and E2F1, modulating their activity. Its expression is regulated by upstream activators including MYC, E2F1, and NF-??B, and signaling cascades such as PI3K/AKT and ERK. Post-translational modifications, including phosphorylation by CK2 and PKC and SUMOylation, fine-tune HDAC1 function. HDAC1 predominantly acts as a transcriptional repressor through association with corepressor complexes like mSin3A, NuRD, and CoREST. Key downstream targets repressed by HDAC1 include the cyclin-dependent kinase inhibitor p21 (CDKN1A), the cell adhesion molecule E-cadherin (CDH1), and the pro-apoptotic Bcl-2 family member Bim (BCL2L11). Through these interactions, HDAC1 directly influences cell cycle control, apoptosis, and epithelial-mesenchymal transition.
In the context of PaTu 8988t cells, HDAC1 overexpression is known to promote proliferation and inhibit apoptosis, in part by silencing CDKN1A and pro-apoptotic factors. The knockout of HDAC1 in this KRAS/TP53-mutant model enables researchers to dissect the contribution of HDAC1 to pancreatic cancer cell growth, survival, and epigenetic reprogramming. This model is particularly valuable for investigating how loss of HDAC1-mediated deacetylation alters tumor suppressor pathways, including p53 and Rb/E2F signaling, and for evaluating the dependency of PDAC cells on HDAC1 activity in the presence of concurrent oncogenic mutations. Furthermore, the polyclonal population allows for the study of heterogeneous responses to HDAC1 disruption, mimicking the complexity of tumor cell populations.
This HDAC1 knockout polyclonal cell product is ideally suited for a range of advanced research applications in cancer epigenetics and pancreatic cancer biology. It can be employed in drug target validation studies and HDAC inhibitor screening assays, using tools such as Western blotting for HDAC1 and histone acetylation markers (e.g., acetyl-H3K9, acetyl-H4K16), RT-qPCR for expression changes of downstream targets (e.g., CDKN1A, CDH1), and ChIP-qPCR to assess histone acetylation at target gene promoters. Functional assays, including MTT or BrdU proliferation assays, flow cytometric analysis of cell cycle and apoptosis, and colony formation assays, can be performed to quantify phenotypic consequences of HDAC1 loss. Additionally, this model supports migration and invasion assays and drug sensitivity testing with clinical HDAC inhibitors such as vorinostat or panobinostat. For further information or to discuss custom projects, please contact Ascent Research.
