Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

OBJECTIVES: To identify gene expression alterations associated with insulinoma formation and progression in 2 mouse models of multiple endocrine neoplasia type 1. METHODS: Mice were killed at 12 or 16 months, and pancreatic islets were isolated by enzymatic and physical disruption. Islets were separated by size representing control, normal, hyperplastic, and adenomous islets. RNA was isolated from these islets and profiled on Sentrix Mouse-6 Expression version 1 BeadChips. Array data were analyzed in GeneSpring. RESULTS: One hundred and one genes that were significantly (P ≤ 0.05) altered in hyperplastic islets and insulinomas compared with normal islets were identified. Of these, 64 gene elements showed reduced messenger RNA levels and 37 gene elements had increased gene expression compared with control islets. Altered expression of 3 genes, namely, Gata6, Tspan8, and s100a8, was confirmed by quantitative reverse transcription-polymerase chain reaction, and aberrant levels of Tspan8 and Lmo2 protein measured by Western blot correlated with the changes in messenger RNA levels. CONCLUSIONS: These results suggest that alterations in gene expression of Gata6, Tspan8, S100a8, and Lmo2 may act via novel pathways that play functionally important roles in Men1-associated tumor progression.

Original publication




Journal article



Publication Date





1140 - 1146


Adaptor Proteins, Signal Transducing, Animals, Antigens, Neoplasm, Blotting, Western, Calgranulin A, DNA-Binding Proteins, Disease Progression, Female, GATA6 Transcription Factor, Gene Expression Profiling, Humans, Insulinoma, Islets of Langerhans, LIM Domain Proteins, Male, Membrane Glycoproteins, Metalloproteins, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Multiple Endocrine Neoplasia Type 1, Oligonucleotide Array Sequence Analysis, Pancreatic Neoplasms, Proto-Oncogene Proteins, Reverse Transcriptase Polymerase Chain Reaction, Tetraspanins