The ASGR1 Knockout T-47D Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed to disrupt the ASGR1 gene in the human T-47D cell line. This loss-of-function model is generated using a polyclonal pool of knockout cells, ensuring a broad representation of editing events without clonal selection. The product serves as a versatile tool for studying ASGR1-dependent pathways in a breast cancer context, where ectopic expression of this liver-specific receptor may influence cellular behavior.
The T-47D host cell line is derived from a pleural effusion of a human breast ductal carcinoma and is widely characterized as an estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, and HER2-negative model. These cells retain hormone responsiveness, making them a relevant system for investigating hormone-dependent signaling in breast cancer. Their origin from metastatic fluid further underscores their utility in modeling advanced disease states and tumor microenvironment interactions.
ASGR1 encodes the major subunit of the asialoglycoprotein receptor, which forms a heterooligomeric complex with ASGR2 to mediate clathrin-dependent endocytosis of desialylated glycoproteins. The receptor interacts with the clathrin adaptor AP-2 and LRP1 for efficient internalization. Transcription of ASGR1 is regulated by estrogen receptor alpha (ESR1) and HNF4??. Its ligands, such as asialofetuin, are targeted for lysosomal degradation, maintaining serum glycoprotein homeostasis. Knockout of ASGR1 abolishes this clearance pathway, leading to accumulation of desialylated glycoproteins and potential dysregulation of downstream signaling.
In the T-47D ER-positive breast cancer model, ASGR1 knockout offers a unique platform to study non-hepatic functions of this receptor. The hormonal regulation by ESR1 allows investigation of estrogen-dependent modulation of glycoprotein clearance in a tumor context. Disruption of ASGR1 may alter the clearance of tumor-derived glycoproteins from the microenvironment, impacting paracrine signaling and immune interactions, and thereby affecting breast cancer progression.
Researchers can employ this polyclonal knockout model in a variety of assays, including western blotting, RT-qPCR, immunofluorescence, and flow cytometry for confirmation and functional studies. Endocytosis assays with fluorescent asialofetuin, glycoprotein clearance assays, and cell proliferation or migration assays can be used to assess the impact on tumor cell behavior. This product is ideal for investigating ectopic ASGR1 function, glycoprotein homeostasis, and endocytic trafficking in breast cancer. For further details, please contact Ascent Research.
