The DKK1 Knockout T-47D Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population generated by disrupting the DKK1 gene in the T-47D human breast cancer cell line. This polyclonal pool provides a heterogeneous knockout model suitable for studying DKK1-dependent phenotypes without the limitations of clonal selection.
The T-47D cell line was derived from a pleural effusion of an infiltrating ductal carcinoma and serves as a well-characterized model of estrogen receptor-positive (ER+) breast cancer. These cells retain hormone responsiveness and express estrogen receptor alpha (ESR1), making them a relevant system for investigating endocrine-related signaling and breast cancer progression.
DKK1 encodes a secreted antagonist of canonical Wnt/??-catenin signaling. DKK1 binds to LRP5 and LRP6 co-receptors and Kremen proteins (KREMEN1, KREMEN2) to trigger internalization of the receptor complex, thereby preventing Wnt ligand-mediated formation of Frizzled-LRP signalosomes. As a result, ??-catenin (CTNNB1) is targeted for degradation, suppressing TCF/LEF-mediated transcription of targets such as MYC, CCND1, and AXIN2. Upstream regulators include WNT3A, CTNNB1, and TP53, while the gene is also transcriptionally influenced by ESR1 and MIR335. Loss of DKK1 disrupts this negative feedback, potentially leading to stabilized ??-catenin and enhanced TCF7/LEF1 activity.
In the T-47D context, CRISPR-mediated disruption of DKK1 may release Wnt pathway inhibition, impacting proliferation, migration, and tumorigenic potential. Given the crosstalk between estrogen receptor and Wnt signaling, this knockout model allows dissection of how DKK1 loss modulates hormone-responsive gene programs and may contribute to mechanisms of breast cancer progression or bone metastasis.
This product is suitable for functional genomics studies, including TOPFlash reporter assays to assess ??-catenin transcriptional activity, Western blotting for ??-catenin and phospho-LRP6, and RT-qPCR analyses of AXIN2 and MYC expression. Further applications include immunofluorescence for ??-catenin subcellular localization, cell proliferation and migration assays, drug target validation for Wnt pathway inhibitors, and high-throughput phenotypic screening. For detailed product specifications, please contact Ascent Research.
