The IGF2 Knockout PaTu 8988t Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human pancreatic adenocarcinoma cell line PaTu 8988t. This product provides a genetically defined loss-of-function model for studying the role of insulin-like growth factor 2 (IGF2) in cancer biology. The polyclonal population preserves the heterogeneity of the parental cells while disrupting the IGF2 gene locus via CRISPR/Cas9-mediated targeted gene disruption, enabling robust functional studies without clonal selection artifacts.
The host cell line PaTu 8988t is a human pancreatic ductal adenocarcinoma epithelial line originally established from a liver metastasis of a pancreatic adenocarcinoma. It harbors a KRAS mutation, a hallmark driver of pancreatic tumorigenesis, and serves as a widely used model for metastatic pancreatic cancer. This cell background recapitulates key molecular features of aggressive PDAC, including constitutive activation of RAS-driven signaling pathways, making it particularly suitable for evaluating the contribution of growth factor signaling in disease progression.
IGF2 encodes a potent fetal growth factor that signals primarily through the type 1 insulin-like growth factor receptor (IGF1R) and the insulin receptor isoform A. Ligand binding induces receptor autophosphorylation and recruitment of adaptor proteins IRS1 and SHC, which in turn activate two major downstream cascades: the PI3K/AKT/mTOR pathway and the RAS/RAF/MEK/ERK pathway. These cascades regulate effectors such as mTOR, S6K, ERK1/2, and FOXO transcription factors to drive cellular proliferation, survival, and metabolic reprogramming. IGF2 expression is tightly controlled by the transcription factor PLAG1, growth hormone, and epigenetic imprinting at the H19/IGF2 locus, while its bioavailability is modulated by interacting partners including IGFBP3 and the clearance receptor IGF2R.
In the PaTu 8988t metastatic pancreatic cancer model, KRAS-driven signaling and IGF2-mediated pathways may converge to reinforce malignant phenotypes. Disrupting IGF2 in this background allows researchers to dissect the contribution of autocrine and paracrine IGF2 signaling to tumor cell proliferation, migration, and survival, and to investigate potential synergy with KRAS effector pathways. This knockout cell population thus represents a valuable tool for elucidating the importance of fetal growth factor reactivation in pancreatic ductal adenocarcinoma progression and for evaluating the therapeutic potential of targeting IGF signaling.
This product is suitable for a wide array of experimental applications, including quantitative assessment of proliferation via MTT or colony formation assays, analysis of cell migration and invasion using Transwell systems, and mechanistic studies of signal transduction by phospho-AKT and phospho-ERK immunoblotting. It also supports in vivo xenograft tumor growth models to monitor tumorigenicity and metastasis, as well as investigations into imprinted gene regulation and the epigenetic control of the H19/IGF2 locus. For detailed technical specifications, validation data, or to discuss customized applications, please contact Ascent Research.
