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Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic epithelial proliferation by Mg(2+)-sensitive Socs3a signaling in development and cancer
Genetic analysis of pancreatic development has provided new insights into the mechanisms underlying the formation of exocrine pancreatic neoplasia. Zebrafish sweetbread (swd) mutants develop hypoplastic acini and dysmorphic ducts in the exocrine pancreas, with impeded progression of cell division cy...
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Formato: | Texto |
Lenguaje: | English |
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The Company of Biologists Limited
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046099/ https://www.ncbi.nlm.nih.gov/pubmed/21183474 http://dx.doi.org/10.1242/dmm.004564 |
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author | Yee, Nelson S. Zhou, Weiqiang Liang, I-Chau |
author_facet | Yee, Nelson S. Zhou, Weiqiang Liang, I-Chau |
author_sort | Yee, Nelson S. |
collection | PubMed |
description | Genetic analysis of pancreatic development has provided new insights into the mechanisms underlying the formation of exocrine pancreatic neoplasia. Zebrafish sweetbread (swd) mutants develop hypoplastic acini and dysmorphic ducts in the exocrine pancreas, with impeded progression of cell division cycle and of epithelial growth. Positional cloning and allelic complementation have revealed that the swd mutations affect the transient receptor potential melastatin-subfamily member 7 (trpm7) gene, which encodes a divalent cation-permeable channel with kinase activity. Supplementary Mg(2+) partially rescued the exocrine pancreatic defects of the trpm7 mutants by improving cell-cycle progression and growth and repressing the suppressor of cytokine signaling 3a (socs3a) gene. The role of Socs3a in Trpm7-mediated signaling is supported by the findings that socs3a mRNA level is elevated in the trpm7 mutants, and antisense inhibition of socs3a expression improved their exocrine pancreatic growth. TRPM7 is generally overexpressed in human pancreatic adenocarcinoma. TRPM7-deficient cells are impaired in proliferation and arrested in the G0-G1 phases of the cell division cycle. Supplementary Mg(2+) rescued the proliferative defect of the TRPM7-deficient cells. Results of this study indicate that Trpm7 regulates exocrine pancreatic development via the Mg(2+)-sensitive Socs3a pathway, and suggest that aberrant TRPM7-mediated signaling contributes to pancreatic carcinogenesis. |
format | Text |
id | pubmed-3046099 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Company of Biologists Limited |
record_format | MEDLINE/PubMed |
spelling | pubmed-30460992011-03-03 Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic epithelial proliferation by Mg(2+)-sensitive Socs3a signaling in development and cancer Yee, Nelson S. Zhou, Weiqiang Liang, I-Chau Dis Model Mech Research Article Genetic analysis of pancreatic development has provided new insights into the mechanisms underlying the formation of exocrine pancreatic neoplasia. Zebrafish sweetbread (swd) mutants develop hypoplastic acini and dysmorphic ducts in the exocrine pancreas, with impeded progression of cell division cycle and of epithelial growth. Positional cloning and allelic complementation have revealed that the swd mutations affect the transient receptor potential melastatin-subfamily member 7 (trpm7) gene, which encodes a divalent cation-permeable channel with kinase activity. Supplementary Mg(2+) partially rescued the exocrine pancreatic defects of the trpm7 mutants by improving cell-cycle progression and growth and repressing the suppressor of cytokine signaling 3a (socs3a) gene. The role of Socs3a in Trpm7-mediated signaling is supported by the findings that socs3a mRNA level is elevated in the trpm7 mutants, and antisense inhibition of socs3a expression improved their exocrine pancreatic growth. TRPM7 is generally overexpressed in human pancreatic adenocarcinoma. TRPM7-deficient cells are impaired in proliferation and arrested in the G0-G1 phases of the cell division cycle. Supplementary Mg(2+) rescued the proliferative defect of the TRPM7-deficient cells. Results of this study indicate that Trpm7 regulates exocrine pancreatic development via the Mg(2+)-sensitive Socs3a pathway, and suggest that aberrant TRPM7-mediated signaling contributes to pancreatic carcinogenesis. The Company of Biologists Limited 2011-03 /pmc/articles/PMC3046099/ /pubmed/21183474 http://dx.doi.org/10.1242/dmm.004564 Text en © 2011. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms |
spellingShingle | Research Article Yee, Nelson S. Zhou, Weiqiang Liang, I-Chau Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic epithelial proliferation by Mg(2+)-sensitive Socs3a signaling in development and cancer |
title | Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic epithelial proliferation by Mg(2+)-sensitive Socs3a signaling in development and cancer |
title_full | Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic epithelial proliferation by Mg(2+)-sensitive Socs3a signaling in development and cancer |
title_fullStr | Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic epithelial proliferation by Mg(2+)-sensitive Socs3a signaling in development and cancer |
title_full_unstemmed | Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic epithelial proliferation by Mg(2+)-sensitive Socs3a signaling in development and cancer |
title_short | Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic epithelial proliferation by Mg(2+)-sensitive Socs3a signaling in development and cancer |
title_sort | transient receptor potential ion channel trpm7 regulates exocrine pancreatic epithelial proliferation by mg(2+)-sensitive socs3a signaling in development and cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046099/ https://www.ncbi.nlm.nih.gov/pubmed/21183474 http://dx.doi.org/10.1242/dmm.004564 |
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