The ACE2 Knockout HGC-27 Polyclonal Cells are a CRISPR/Cas9-mediated gene-disrupted polyclonal population derived from the human gastric carcinoma cell line HGC-27, engineered for loss-of-function studies of the angiotensin-converting enzyme 2 (ACE2) gene. This polyclonal knockout model avoids clonal selection, providing a genetically diverse cellular pool for investigating ACE2-dependent mechanisms without bias. It enables examination of ACE2??s dual role as a carboxypeptidase in the renin?angiotensin system (RAS) and as the primary receptor for SARS?CoV?2.
The parental HGC-27 cell line originates from the lymph node metastasis of an undifferentiated gastric carcinoma and displays adherent epithelial morphology. It serves as a robust in vitro model for human gastric adenocarcinoma, supporting research into cancer cell signaling, metastasis, and tumor?stromal interactions. The endogenous expression of key RAS components in HGC-27 cells offers a physiologically relevant backdrop for ACE2 knockout studies.
ACE2 is a carboxypeptidase that converts angiotensin II (Ang II) to angiotensin?(1?7) (Ang?(1?7)), which then activates the Mas receptor to promote vasodilation, anti?inflammation, and anti?fibrosis, counteracting the ACE/Ang II/AT1 receptor axis. ACE2 also binds the SARS?CoV?2 spike protein, facilitating viral entry. Its expression is regulated by interferon???/??, interferon???, tumor necrosis factor, and transcription factors such as GATA4 and HNF1??. Additionally, ACE2 interacts with ADAM17 (sheddase), the AT1 receptor, and the amino acid transporter SLC6A19, forming a hub within the RAS and COVID?19 entry networks.
In gastric adenocarcinoma, ACE2 may modulate tumor growth, migration, and the inflammatory microenvironment through local angiotensin peptide metabolism. The HGC-27 ACE2 polyclonal knockout cells enable dissection of these tumor?cell?intrinsic functions and assessment of RAS?targeted therapies. Furthermore, as gastric epithelial cells express ACE2, this model is valuable for studying SARS?CoV?2 tropism, viral entry mechanisms, and gastrointestinal aspects of COVID?19, as well as for antiviral drug screening.
Applications include standard gene?expression and protein analyses via RT?qPCR, western blotting, immunofluorescence, and flow cytometry. Functional assays such as SARS?CoV?2 pseudovirus entry, angiotensin II conversion, wound healing migration, and cell proliferation assays further expand its utility for mechanistic investigation and drug discovery. Researchers can apply this model to explore ACE2?dependent signaling in gastric cancer, screen potential RAS modulators, or develop SARS?CoV?2 entry inhibitors. For additional information, please contact Ascent Research.