KRJ-I and BON Cell Lines: Defining an Appropriate Enterochromaffin Cell Neuroendocrine Tumor Model

作者：Zakiya-Luna Siddique, Ignat Drozdov, Jared Floch, Björn Gustafsson, Kamilla Stunes, Roswitha Pfragner, Mark Kidd, Irvin M. Modlin · 发表于：Neuroendocrinology · 年份：2009 · DOI：10.1159/000209330 · 被引用次数：44 · 研究领域：Neuroendocrine Tumor Research Advances、Gastrointestinal Tumor Research and Treatment、Gastrointestinal disorders and treatments

BACKGROUND: Neuroendocrine tumors (NETs) of the gastrointestinal (GI) system are increasing in incidence with minimal improvement in prognosis. Although the cell of origin has been identified as the enterochromaffin (EC) cell, its secretory and proliferative regulation has not been defined at a mechanistic level. To date, the BON cell line has been the most widely used in vitro EC cell model despite its pancreatic origin. Using whole-genome mathematical analysis as well as secretory and proliferative studies, we compared the BON cell line to the small intestine (SI) EC cell-derived NET cell line, KRJ-I, to assess individual cell line validity and applicability for the investigation of GI-NET disease. METHODS AND RESULTS: Principal component analysis and ANOVA of KRJ-I and BON transcriptomes (U133 Plus 2) identified substantially different (<10%) overlap in transcripts with minimal (R(2) = 0.24) correlation in gene expression profiles. RT-PCR detected large variability (>12%) in neuroendocrine (NE) marker transcripts in the BON cell line and the absence of Tph-2, DDC, TGFbetaR2, and M3 transcripts in KRJ-I. The KRJ-I cell line secreted serotonin (5-HT) in response to isoproterenol (EC(50) = 100 nM), noradrenaline (EC(50) = 1.7 nM), and pituitary adenylate cyclase (PACAP, EC(50) = 0.03 nM). Cholecystokinin (IC(50) = 430 nM), somatostatin (IC(50) = 400 nM), acetylcholine (IC(50) = 3.7 nM), and gamma-aminobutyric acid A (GABA(A), IC(50) = 2 nM) all inhibited 5-HT release, while g...