The IGFBP5 Knockout SK-OV-3 Polyclonal Cells provide a CRISPR/Cas9-edited polyclonal population of SK-OV-3 human ovarian adenocarcinoma cells with disrupted IGFBP5 gene function. This loss-of-function model, generated without clonal selection, preserves heterogeneous editing events typical of polyclonal pools, enabling studies of gene function in a context that mirrors diverse knockout outcomes. The targeted gene encodes insulin-like growth factor-binding protein 5, a modulator of IGF-mediated signaling and cellular processes relevant to cancer progression.
The parental SK-OV-3 cell line, derived from the ascites of an ovarian adenocarcinoma patient, is a well-characterized model of high-grade serous ovarian cancer. These cells are tumorigenic and exhibit intrinsic chemoresistance, recapitulating clinical obstacles. SK-OV-3 harbors mutations in TP53 and activates multiple oncogenic pathways, including PI3K/AKT and MAPK/ERK, making it an ideal host for studying mechanisms driving ovarian cancer malignancy.
IGFBP5 binds IGF1 and IGF2 with high affinity, controlling their availability to activate insulin-like growth factor 1 receptor (IGF1R) and subsequent downstream signaling through AKT1, MAPK1/3, and associated effectors such as BAX, BCL2, and CDKN1A. Transcriptional regulation of IGFBP5 involves TP53, TGFB1, SMAD proteins, and SP1, linking it to p53-dependent apoptosis and TGF-??-mediated growth control. IGFBP5 also interacts with integrin ??V??3, LRP1, and extracellular matrix components, influencing cell adhesion and motility independently of IGFs. Consequently, IGFBP5 serves as a node integrating hormonal, survival, and migratory signals.
Knockout of IGFBP5 in SK-OV-3 disrupts both canonical IGF signaling and context-dependent pathways, potentially reducing AKT and ERK phosphorylation, altering BCL2 family-dependent apoptosis, and modulating p53 transcriptional activity. This intervention may impair pro-survival adaptations and chemoresistance typical of SK-OV-3, while also affecting TGF-??-induced epithelial-mesenchymal transition and integrin-mediated invasion. Thus, the polyclonal knockout model offers a platform to dissect how loss of IGFBP5 reshapes tumorigenic properties and therapeutic vulnerabilities.
Applications include ovarian cancer biology, IGF signaling dissection, drug resistance studies, and metastasis research. Typical assays suited to this model encompass Western blotting for phospho-AKT/ERK, cell viability (MTS), colony formation, Annexin V apoptosis detection, and transwell migration/invasion. In vivo, the cells can be employed in xenograft tumor growth experiments to evaluate the role of IGFBP5 in tumor initiation and progression. For further details, contact Ascent Research.
