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Kmt2a cooperates with menin to suppress tumorigenesis in mouse pancreatic islets

The reported incidence of pancreatic neuroendocrine tumors (PanNETs) has increased, due in large part to improvements in detection and awareness. However, therapeutic options are limited and a critical need exists for understanding a more thorough characterization of the molecular pathology underlyi...

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Autores principales: Lin, Wenchu, Francis, Joshua M., Li, Hong, Gao, Xiaoping, Pedamallu, Chandra Sekhar, Ernst, Patricia, Meyerson, Matthew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5199165/
https://www.ncbi.nlm.nih.gov/pubmed/27801610
http://dx.doi.org/10.1080/15384047.2016.1250986
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author Lin, Wenchu
Francis, Joshua M.
Li, Hong
Gao, Xiaoping
Pedamallu, Chandra Sekhar
Ernst, Patricia
Meyerson, Matthew
author_facet Lin, Wenchu
Francis, Joshua M.
Li, Hong
Gao, Xiaoping
Pedamallu, Chandra Sekhar
Ernst, Patricia
Meyerson, Matthew
author_sort Lin, Wenchu
collection PubMed
description The reported incidence of pancreatic neuroendocrine tumors (PanNETs) has increased, due in large part to improvements in detection and awareness. However, therapeutic options are limited and a critical need exists for understanding a more thorough characterization of the molecular pathology underlying this disease. The Men1 knockout mouse model recapitulates the early stage of human PanNET development and can serve as a foundation for the development of advanced mouse models that are necessary for preclinical testing. Menin, the product of the MEN1 gene, has been shown to physically interact with the KMT2A and KMT2B histone methyltransferases. Both the KMT2A and MEN1 genes are located on chromosome 11q, which frequently undergoes loss of heterozygosity (LOH) in PanNETs. We report herein that inactivation of Kmt2a in Men1-deficient mice accelerated pancreatic islet tumorigenesis and shortened the average life span. Increases in cell proliferation were observed in mouse pancreatic islet tumors upon inactivation of both Kmt2a and Men1. The Kmt2a/Men1 double knockout mouse model can be used as a mouse model to study advanced PanNETs.
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spelling pubmed-51991652016-12-30 Kmt2a cooperates with menin to suppress tumorigenesis in mouse pancreatic islets Lin, Wenchu Francis, Joshua M. Li, Hong Gao, Xiaoping Pedamallu, Chandra Sekhar Ernst, Patricia Meyerson, Matthew Cancer Biol Ther Research Paper The reported incidence of pancreatic neuroendocrine tumors (PanNETs) has increased, due in large part to improvements in detection and awareness. However, therapeutic options are limited and a critical need exists for understanding a more thorough characterization of the molecular pathology underlying this disease. The Men1 knockout mouse model recapitulates the early stage of human PanNET development and can serve as a foundation for the development of advanced mouse models that are necessary for preclinical testing. Menin, the product of the MEN1 gene, has been shown to physically interact with the KMT2A and KMT2B histone methyltransferases. Both the KMT2A and MEN1 genes are located on chromosome 11q, which frequently undergoes loss of heterozygosity (LOH) in PanNETs. We report herein that inactivation of Kmt2a in Men1-deficient mice accelerated pancreatic islet tumorigenesis and shortened the average life span. Increases in cell proliferation were observed in mouse pancreatic islet tumors upon inactivation of both Kmt2a and Men1. The Kmt2a/Men1 double knockout mouse model can be used as a mouse model to study advanced PanNETs. Taylor & Francis 2016-11-01 /pmc/articles/PMC5199165/ /pubmed/27801610 http://dx.doi.org/10.1080/15384047.2016.1250986 Text en © 2016 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Research Paper
Lin, Wenchu
Francis, Joshua M.
Li, Hong
Gao, Xiaoping
Pedamallu, Chandra Sekhar
Ernst, Patricia
Meyerson, Matthew
Kmt2a cooperates with menin to suppress tumorigenesis in mouse pancreatic islets
title Kmt2a cooperates with menin to suppress tumorigenesis in mouse pancreatic islets
title_full Kmt2a cooperates with menin to suppress tumorigenesis in mouse pancreatic islets
title_fullStr Kmt2a cooperates with menin to suppress tumorigenesis in mouse pancreatic islets
title_full_unstemmed Kmt2a cooperates with menin to suppress tumorigenesis in mouse pancreatic islets
title_short Kmt2a cooperates with menin to suppress tumorigenesis in mouse pancreatic islets
title_sort kmt2a cooperates with menin to suppress tumorigenesis in mouse pancreatic islets
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5199165/
https://www.ncbi.nlm.nih.gov/pubmed/27801610
http://dx.doi.org/10.1080/15384047.2016.1250986
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