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Title

Pancreatic beta-cell-specific ablation of the multiple endocrine neoplasia type 1 (MEN1) gene causes full penetrance of insulinoma development in mice

Authors
Bertolino, Philippe
Tong, W. M.
Casse, Huguette
Zhang, C. X.
Wang, Z. Q.
Published in Cancer Research. 2003, vol. 63, no. 16, p. 4836-4841
Abstract The function of the predisposition gene to multiple endocrine neoplasia type 1 (MEN1) syndrome remains largely unknown. Previous studies demonstrated that null mutation of the Men1 gene caused mid-gestation lethality in mice, whereas heterozygous Men1 knockout mice developed multiple endocrine tumors late in life. To seek direct evidence on the causal role of menin in suppressing tumor development, we generated mice in which the Men1 gene was disrupted specifically in pancreatic beta cells. These mice began to develop hyperplastic islets at as early as 2 months of age and insulinomas at 6 months of age. The islet lesions exhibited features of multistage tumor progression, including beta-cell dedifferentiation, angiogenesis, and altered expression of both E-cadherin and beta-catenin. Additionally, disturbance of blood insulin and glucose levels correlated with tumor development, mimicking human MEN1 symptoms. Our data indicate that this strain of mice provides a powerful tool for the study of the mechanisms of tumorigenesis related to MEN1 disease.
Keywords AnimalsBlood Glucose/analysisCytoskeletal Proteins/analysisGene DeletionInsulin/bloodInsulinoma/ etiologyIslets of Langerhans/ metabolismMiceMice, KnockoutNeoplasm Proteins/ geneticsPancreatic Neoplasms/ etiologyProto-Oncogene ProteinsTrans-Activators/analysisBeta Catenin
Identifiers
PMID: 12941803
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Research group Types cellulaires pancréatiques pendant l'ontogénèse (522)
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BERTOLINO, Philippe et al. Pancreatic beta-cell-specific ablation of the multiple endocrine neoplasia type 1 (MEN1) gene causes full penetrance of insulinoma development in mice. In: Cancer Research, 2003, vol. 63, n° 16, p. 4836-4841. https://archive-ouverte.unige.ch/unige:8640

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Deposited on : 2010-07-12

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