Functional Consequence of β-Arrestin 1 Gene Knock-Out in Pancreatic Neuroendocrine Tumor Cell Line BON-1 Abstract #3047

Introduction: An important limiting factor influencing treatment efficacy of neuroendocrine tumors (NETs) with somatostatin analogs (SSA) is the availability of somatostatin receptors (SSTR) on NETs. While downregulation or altered pattern of SSTR expression are important considerations, receptor internalization/desensitization by β-arrestins may be a crucial contributing factor. Interestingly, our previous study showed a preferential higher expression of β-arrestin 1 (ARRB1), in gastroenteropancreatic NETS (GEP-NETs) compared to pituitary adenomas.
Aim(s): The present research investigates the functional consequence of the knock-out of β-arrestin 1 using CRISPR-Cas9 in the BON-1 pancreatic neuroendocrine tumor (Pan-NET) cell model.
Materials and methods: BON-1 cells were co-transfected with lentiviral plasmids encoding Cas9 and sgRNA directed against ARRB1. Clonal populations (n=52) of the cells, generated by limiting dilution, were screened for the presence of indels in ARRB1 by Sanger Sequencing. Absence of functional β-arrestin 1 protein in selected clones was confirmed by Western Blot. The clones were assessed for their growth characteristics and sensitivity to SSAs octreotide and pasreotide.
Conference: 17th Annual ENETS Conference 2020 (2020)
Category: Basic Science - Signaling pathways, receptors, biomarkers
Presenting Author: Dr Anand Iyer

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