The IGF2 Knockout A2780 Polyclonal Cells are a CRISPR/Cas9-mediated knockout cell population engineered from the A2780 human ovarian cancer line. This product comprises a polyclonal pool, providing a diverse representation of gene-edited alleles for robust loss-of-function experiments. Disruption of the fetal growth factor IGF2 eliminates its ligand activity, enabling investigation of IGF2-dependent processes in epithelial ovarian carcinoma.
The A2780 cell line was derived from an untreated patient with ovarian endometrioid adenocarcinoma and is characterized by wild-type p53 and sensitivity to platinum-based chemotherapy. It is a well-established in vitro model for endometrioid ovarian carcinoma, the most common type I ovarian tumor, and recapitulates key molecular features including relatively slow proliferation and intact apoptosis pathways.
IGF2 is a potent growth factor that signals through IGF1R and the insulin receptor to promote proliferation, survival, and metabolic reprogramming. Ligand binding triggers IRS1 phosphorylation, leading to activation of the PI3K/AKT and RAS-RAF-MEK-ERK1/2 pathways. AKT-mediated signaling activates mTORC1 and S6K while inhibiting pro-apoptotic BAD and FOXO1, thereby enhancing protein synthesis and cell viability. The RAS-MAPK cascade further drives cell cycle progression. IGF2 expression is regulated by the H19 lncRNA, CTCF-bound imprinting control regions, PLAG1, and STAT3, and its extracellular availability is controlled by six IGF-binding proteins (IGFBP1-6), the scavenger receptor IGF2R, and interactions with integrin ??v??3 and vitronectin.
In A2780 cells, autocrine and paracrine IGF2 stimulation contributes to ovarian cancer progression, supporting uncontrolled growth and resistance to apoptosis, including that induced by platinum agents. The IGF2 knockout in this platinum-sensitive background provides a unique tool to interrogate the contribution of imprinted gene dysregulation to disease pathogenesis and to explore mechanisms of chemoresistance. Furthermore, this model is pertinent for studying growth restriction disorders and other IGF2-related cancers such as colorectal and breast carcinomas.
These polyclonal knockout cells facilitate a wide range of assays: western blotting for phosphorylated AKT (Ser473) and ERK1/2 (Thr202/Tyr204) to assess pathway activity; RT-qPCR for IGF2 transcript quantification; MTT and Annexin V flow cytometry for proliferation and apoptosis; dose-response curves for cisplatin and paclitaxel to evaluate drug sensitivity; and soft agar assays for anchorage-independent growth. In vivo tumorigenicity can be examined via subcutaneous xenografts in immunodeficient mice. They are also suited for testing IGF1R inhibitors and other targeted therapeutics. For further information, please contact Ascent Research.
