Description

The FOXA1 Knockout Lncap Cell Line is a CRISPR/Cas9-edited knockout cell line that disrupts the FOXA1 gene in the Lncap human prostate carcinoma epithelial cell line. This loss-of-function model enables detailed investigation of FOXA1-dependent regulatory mechanisms in an androgen-sensitive context, providing a robust platform for studying pioneer transcription factor activity in hormone-mediated transcription and prostate cancer progression.

The parental Lncap cell line was derived from a needle aspiration biopsy of a lymph node metastasis from a patient with prostate adenocarcinoma. These cells are androgen receptor (AR)-positive, secrete prostate-specific antigen (PSA), and exhibit androgen-dependent growth, making them a canonical model for AR signaling and hormone-responsive tumor biology. Lncap cells retain characteristic luminal epithelial features and are widely used in anti-androgen drug testing, including responses to enzalutamide and bicalutamide.

FOXA1 is a pioneer transcription factor that binds compacted chromatin to facilitate AR recruitment to regulatory regions of target genes, driving hormone-mediated transcriptional programs essential for prostate epithelial differentiation and tumor progression. It interacts with cofactors such as GATA2, the SWI/SNF complex, and MED1, and is regulated by upstream inputs including AR, estrogen receptor alpha, the ERK/MAPK pathway, and the PI3K/AKT pathway. FOXA1 transcriptionally regulates key downstream targets such as KLK3 (PSA), TMPRSS2, and NKX3-1, as well as cell cycle regulators, thereby controlling proliferation and differentiation.

In Lncap cells, FOXA1 is a critical mediator of androgen-dependent transcription. Disruption of FOXA1 abrogates AR-mediated gene induction, including PSA expression, and impairs hormone-driven growth and differentiation. This knockout model enables dissection of FOXA1-dependent versus FOXA1-independent AR functions and exploration of hormone sensitivity and resistance mechanisms. It provides a physiologically relevant system to study the dependency of oncogenic pathways on pioneer factor activity in a metastasis-derived epithelial background.

The cell line supports a wide range of applications: investigating AR signaling dependency on FOXA1, profiling transcriptomic changes via RNA-seq and RT-qPCR, mapping chromatin occupancy with ChIP-seq, and assessing cellular phenotypes through proliferation, migration, and invasion assays. It is also valuable for anti-androgen drug sensitivity testing (e.g., enzalutamide, bicalutamide) and cell cycle analysis. For further details or to inquire about this product, please contact Ascent Research.