Description

The Grn Knockout Py8119 Cell Line is a CRISPR/Cas9-edited knockout cell line designed to disrupt progranulin (Grn) gene expression in the mouse Py8119 mammary carcinoma epithelial cell background. This stable loss-of-function model provides a consistent and reliable system for investigating progranulin-dependent phenotypes in cancer biology and signaling research.

The Py8119 cell line was established from a C57BL/6 mammary carcinoma driven by the MMTV-PyMT transgene. These tumorigenic epithelial cells recapitulate key features of human breast cancer, including invasive growth and metastatic potential, and are widely employed in syngeneic transplantation models to study tumor biology in an immunocompetent setting.

Progranulin, the product of the Grn gene, is a secreted growth factor that engages TNFRSF1A, TNFRSF1B, and EPHA2 receptors on Py8119 cells, activating the PI3K/AKT/mTOR and MAPK/ERK signaling axes. This leads to phosphorylation of AKT and ERK1/2, subsequent NF-??B activation, and transcriptional upregulation of cyclin D1 and Bcl-2, fostering proliferation, survival, and motility. Transcriptional control of Grn is mediated by c-Myc, SP1, TNF-??, and HIF-1??, while SORT1 modulates progranulin localization and turnover. Through these interactions, progranulin integrates oncogenic and microenvironmental signals to sustain mammary carcinoma progression.

In the Py8119 mammary carcinoma line, ablation of Grn disrupts progranulin-mediated stimulation of key oncogenic pathways, providing a clean genetic tool to interrogate progranulin??s contribution to tumor aggressiveness. This knockout model is anticipated to show diminished AKT and ERK pathway activity, reduced cyclin D1 and Bcl-2 levels, and impaired migratory and invasive behavior, allowing systematic dissection of downstream molecular mechanisms. Because Py8119 is syngeneic to C57BL/6, the knockout line can be employed in immunocompetent orthotopic transplantation studies to examine the interplay between tumor-derived progranulin and host stromal and immune cells.

Applications of the Grn Knockout Py8119 Cell Line span detailed signaling pathway investigations, drug screening for progranulin-addicted tumors, and functional studies of breast cancer metastasis and microenvironmental interactions. The model supports a wide range of assays including RT?qPCR, Western blotting, cell proliferation and transwell migration/invasion analyses, flow cytometry for apoptosis, and phospho-signaling profiling, enabling robust pharmacodynamic and mechanistic readouts. For further information, please contact Ascent Research.