The MEN1 Knockout HK-2 Cell Line is a genetically engineered human cell model generated via CRISPR/Cas9-mediated disruption of the MEN1 locus in the HK-2 proximal tubule epithelial cell line. This product is provided as a ready-to-use knockout cell line, enabling rigorous loss-of-function studies of the tumor suppressor protein menin. The editing strategy introduces targeted gene disruption to ablate menin expression, offering researchers a stable and reproducible system for investigating MEN1-dependent cellular processes. As a component of our expanding portfolio of gene-edited renal cell models, this knockout cell line is designed to support advanced biomedical research applications, including cancer biology, signal transduction, and epigenetic regulation studies.
The host cell line, HK-2, is an immortalized normal human kidney proximal tubule epithelial cell line derived from adult human renal cortex. These cells retain many functional characteristics of their in vivo counterparts, including solute reabsorption, maintenance of acid-base balance, and secretion functions critical to renal physiology. HK-2 cells are widely employed as a non-transformed renal epithelial model to study nephrotoxicity, tubular transport mechanisms, and disease-related changes in kidney function. Their well-documented growth properties and responsiveness to physiological stimuli make them an ideal background for examining the role of tumor suppressors like MEN1 in a renal context, where proximal tubule cells represent a key site of injury, repair, and malignant transformation.
Menin, encoded by the MEN1 gene, is a ubiquitously expressed scaffold protein that orchestrates diverse nuclear processes by tethering multiple transcriptional regulators and chromatin-modifying complexes. It serves as an integral subunit of MLL1/MLL2 (KMT2A/KMT2B) histone methyltransferase complexes, directly interacting with LEDGF, JunD, NF-??B, Smad3, FANCD2, and PTIP to coordinate gene expression, DNA damage repair, and cell cycle progression. Menin functions downstream of TGF-?? receptor activation, where it partners with Smad2/3 to transcriptionally regulate targets such as the cyclin-dependent kinase inhibitors CDKN1B (p27) and CDKN2C (p18). Additionally, menin??s activity is modulated post-translationally by AKT-mediated phosphorylation and transcriptionally by microRNAs miR-24 and miR-34a.
Through these interactions, menin promotes repressive and activating histone marks, notably H3K4me3 deposition at promoters of key growth-regulatory genes, thereby exerting its tumor-suppressive functions. In the renal proximal tubule epithelium, loss of menin disrupts critical homeostatic pathways, including TGF-??/Smad-mediated growth inhibition and PI3K/AKT survival signaling, which are frequently dysregulated during renal cell carcinoma (RCC) development. Although MEN1 mutations are classically associated with multiple endocrine neoplasia type 1, emerging evidence implicates menin in the pathogenesis of sporadic renal tumors, making this HK-2 knockout model highly relevant for dissecting early events in kidney carcinogenesis. The cell line enables detailed investigation of how menin deficiency alters chromatin landscape, DNA damage responses, and cell cycle control in a nontransformed epithelial setting, thereby providing a platform to study the transition from normal epithelia to a precancerous state.
Typical research applications for the MEN1 Knockout HK-2 Cell Line include functional rescue experiments, drug sensitivity profiling with menin inhibitors, and mechanistic studies of chromatin regulation through techniques such as ChIP-qPCR targeting H3K4me3 and western blotting of downstream effectors. The model is highly suited for cell proliferation and colony formation assays to assess tumor-suppressive capacity, as well as flow cytometry for cell cycle distribution analysis. Furthermore, it serves as an excellent tool for exploring TGF-?? signal transduction and for screening compounds that modulate menin?CMLL interactions. For detailed validation data and technical support, please contact Ascent Research.
